Publications
2014
Blond A, Ennifar E, Tisné C, Micouin L
The Design of RNA Binders: Targeting the HIV Replication Cycle as a Case Study. Article de journal
Dans: ChemMedChem, vol. 9, no. 9, p. 1982-96, 2014, ISBN: 25100137.
Résumé | Liens | BibTeX | Étiquettes: DUMAS, ENNIFAR, RNA recognition antiviral agents drug design human immunodeficiency virus new targets, Unité ARN
@article{,
title = {The Design of RNA Binders: Targeting the HIV Replication Cycle as a Case Study.},
author = {A Blond and E Ennifar and C Tisné and L Micouin},
url = {http://www.ncbi.nlm.nih.gov/pubmed/25100137?dopt=Abstract},
doi = {10.1002/cmdc.201402259},
isbn = {25100137},
year = {2014},
date = {2014-01-01},
journal = {ChemMedChem},
volume = {9},
number = {9},
pages = {1982-96},
abstract = {The human immunodeficiency virus 1 (HIV-1) replication cycle is finely tuned with many important steps involving RNA-RNA or protein-RNA interactions, all of them being potential targets for the development of new antiviral compounds. This cycle can also be considered as a good benchmark for the evaluation of early-stage strategies aiming at designing drugs that bind to RNA, with the possibility to correlate in vitro activities with antiviral properties. In this review, we highlight different approaches developed to interfere with four important steps of the HIV-1 replication cycle: the early stage of reverse transcription, the transactivation of viral transcription, the nuclear export of partially spliced transcripts and the dimerization step.},
keywords = {DUMAS, ENNIFAR, RNA recognition antiviral agents drug design human immunodeficiency virus new targets, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Košutić M, Jud L, Veiga C Da, Frener M, Fauster K, Kreutz C, Ennifar E, Micura R
Surprising base pairing and structural properties of 2'-trifluoromethylthio-modified ribonucleic acids. Article de journal
Dans: J Am Chem Soc, vol. 136, no. 18, p. 6656-63, 2014, ISBN: 24766131.
Résumé | Liens | BibTeX | Étiquettes: DUMAS, ENNIFAR, Unité ARN
@article{,
title = {Surprising base pairing and structural properties of 2'-trifluoromethylthio-modified ribonucleic acids.},
author = {M Košutić and L Jud and C Da Veiga and M Frener and K Fauster and C Kreutz and E Ennifar and R Micura},
url = {http://www.ncbi.nlm.nih.gov/pubmed/24766131?dopt=Abstract},
doi = {10.1021/ja5005637},
isbn = {24766131},
year = {2014},
date = {2014-01-01},
journal = {J Am Chem Soc},
volume = {136},
number = {18},
pages = {6656-63},
abstract = {The chemical synthesis of ribonucleic acids (RNA) with novel chemical modifications is largely driven by the motivation to identify eligible functional probes for the various applications in life sciences. To this end, we have a strong focus on the development of novel fluorinated RNA derivatives that are powerful in NMR spectroscopic analysis of RNA folding and RNA ligand interactions. Here, we report on the synthesis of 2'-SCF3 pyrimidine nucleoside containing oligoribonucleotides and the comprehensive investigation of their structure and base pairing properties. While this modification has a modest impact on thermodynamic stability when it resides in single-stranded regions, it was found to be destabilizing to a surprisingly high extent when located in double helical regions. Our NMR spectroscopic investigations on short single-stranded RNA revealed a strong preference for C2'-endo conformation of the 2'-SCF3 ribose unit. Together with a recent computational study (L. Li, J. W. Szostak, J. Am. Chem. Soc. 2014, 136, 2858-2865) that estimated the extent of destabilization caused by a single C2'-endo nucleotide within a native RNA duplex to amount to 6 kcal mol(-1) because of disruption of the planar base pair structure, these findings support the notion that the intrinsic preference for C2'-endo conformation of 2'-SCF3 nucleosides is most likely responsible for the pronounced destabilization of double helices. Importantly, we were able to crystallize 2'-SCF3 modified RNAs and solved their X-ray structures at atomic resolution. Interestingly, the 2'-SCF3 containing nucleosides that were engaged in distinct mismatch arrangements, but also in a standard Watson-Crick base pair, adopted the same C3'-endo ribose conformations as observed in the structure of the unmodified RNA. Likely, strong crystal packing interactions account for this observation. In all structures, the fluorine atoms made surprisingly close contacts to the oxygen atoms of the corresponding pyrimidine nucleobase (O2), and the 2'-SCF3 moieties participated in defined water-bridged hydrogen-bonding networks in the minor groove. All these features allow a rationalization of the structural determinants of the 2'-SCF3 nucleoside modification and correlate them to base pairing properties.},
keywords = {DUMAS, ENNIFAR, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2013
Bec G, Meyer B, Gerard M A, Steger J, Fauster K, Wolff P, Burnouf D, Micura R, Dumas P, Ennifar E
Thermodynamics of HIV-1 Reverse Transcriptase in action elucidates the mechanism of action of non-nucleoside inhibitors. Article de journal
Dans: J Am Chem Soc, vol. 135, no. 26, p. 9743-9752, 2013, ISBN: 23742167.
Résumé | Liens | BibTeX | Étiquettes: DUMAS, ENNIFAR, Unité ARN
@article{,
title = {Thermodynamics of HIV-1 Reverse Transcriptase in action elucidates the mechanism of action of non-nucleoside inhibitors.},
author = {G Bec and B Meyer and M A Gerard and J Steger and K Fauster and P Wolff and D Burnouf and R Micura and P Dumas and E Ennifar},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23742167},
isbn = {23742167},
year = {2013},
date = {2013-01-01},
journal = {J Am Chem Soc},
volume = {135},
number = {26},
pages = {9743-9752},
abstract = {HIV-1 reverse transcriptase (RT) is a heterodimeric enzyme that converts the genomic viral RNA into proviral DNA. Despite intensive biochemical and structural studies, direct thermodynamic data regarding RT interactions with its substrates are still lacking. Here we addressed the mechanism of action of RT and of non-nucleoside RT inhibitors (NNRTIs) by isothermal titration calorimetry (ITC). Using a new incremental-ITC approach, a step-by-step thermody-namic dissection of the RT polymerization activity showed that most of the driving force for DNA synthesis is provided by initial dNTP binding. Surprisingly, thermodynamic and kinetic data led to a re-interpretation of the mechanism of inhibition of NNRTIs. Binding of NNRTIs to preformed RT/DNA complexes is hindered by a kinetic barrier and NNRTIs mostly interact with free RT. Once formed, RT/NNRTI complexes bind DNA either in a seemingly polymerase-competent orientation, or form high-affinity dead-end complexes, both RT/NNRTI/DNA complexes being unable to bind the incoming nucleotide substrate.},
keywords = {DUMAS, ENNIFAR, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Ennifar E
X-ray crystallography as a tool for mechanism-of-action studies and drug discovery Article de journal
Dans: Curr Pharm Biotechnol, vol. 14, no. 5, p. 537-550, 2013, ISBN: ISBN/1389-2010 (Print) 1873-4316 (Online).
Résumé | Liens | BibTeX | Étiquettes: Drug design Ligand Molecular mechanism Protein RNA Structural biology X-ray crystallography, DUMAS, ENNIFAR, Unité ARN
@article{,
title = {X-ray crystallography as a tool for mechanism-of-action studies and drug discovery},
author = {E Ennifar},
url = {http://www.ingentaconnect.com/content/ben/cpb/2013/00000014/00000005/art00007?crawler=true},
isbn = {ISBN/1389-2010 (Print)
1873-4316 (Online)},
year = {2013},
date = {2013-01-01},
journal = {Curr Pharm Biotechnol},
volume = {14},
number = {5},
pages = {537-550},
abstract = {Knowledge of three-dimensional structures of biological macromolecules is essential for a complete understanding of many biological processes. X-ray crystallography is the most widely used technique in structural biology and can provide highly detailed structures of proteins, nucleic acids or macromolecular complexes without any size limit. In the past decade, several recent advances in biological crystallography and automation of data collection and structure solution allowed extraordinary progresses and now more than 58 000 crystal structures have been deposited into the Protein Data Bank. This wealth of structural data significantly helped the elucidation of many biological processes and led to the development of new drugs. In this review we will show how of X-ray crystallography can provide insights into the mechanism of action of biological processes and can contribute to the rationale development of ligands through structure-based drug design.},
keywords = {Drug design Ligand Molecular mechanism Protein RNA Structural biology X-ray crystallography, DUMAS, ENNIFAR, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Ennifar E, Aslam M W, Strasser P, Hoffmann G, Dumas P, van Delft F L
Structure-guided Discovery of a Novel Aminoglycoside Conjugate Targeting HIV-1 RNA Viral Genome. Article de journal
Dans: ACS Chem Biol, vol. 8, no. 11, p. 2509-17, 2013, ISBN: 24015986.
Résumé | Liens | BibTeX | Étiquettes: DUMAS, ENNIFAR, Unité ARN
@article{,
title = {Structure-guided Discovery of a Novel Aminoglycoside Conjugate Targeting HIV-1 RNA Viral Genome.},
author = {E Ennifar and M W Aslam and P Strasser and G Hoffmann and P Dumas and F L van Delft},
url = {http://www.ncbi.nlm.nih.gov/pubmed/24015986?dopt=Abstract},
doi = {10.1021/cb400498n},
isbn = {24015986},
year = {2013},
date = {2013-01-01},
journal = {ACS Chem Biol},
volume = {8},
number = {11},
pages = {2509-17},
abstract = {The Dimerization Initiation Site (DIS) of the HIV-1 genomic RNA is a conserved stem-loop that promotes viral genome dimerization by forming a loop-loop complex. The DIS constitutes a potentially interesting target since it is crucial for several key steps of the viral replication. In this work we describe the synthesis of a rationally designed aminoglycoside conjugate that binds the HIV-1 DIS viral RNA with high specificity, as shown by an extensive in vitro binding characterization. We propose a three-dimensional model of the drug/RNA interaction that perfectly fits with binding data. Our results show the feasibility of targeting the HIV DIS viral RNA dimer and open the way to the rationale design of a new class of antiviral drugs. In addition, due to similarities between the HIV-1 DIS RNA and the bacterial aminoacyl decoding site (A site) RNA, we show that this novel aminoglycoside conjugate also binds the bacterial A site with a similar affinity than natural aminoglycoside antibiotics.},
keywords = {DUMAS, ENNIFAR, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Pendem N, Nelli Y R, Douat C, Fischer L, Laguerre M, Ennifar E, Kauffmann B, Guichard G
Controlling Helix Formation in the γ-Peptide Superfamily: Heterogeneous Foldamers with Urea/Amide and Urea/Carbamate Backbones Article de journal
Dans: Angew Chem Int Ed Engl, vol. 52, no. 15, p. 4147-51, 2013, ISBN: 23460200.
Résumé | Liens | BibTeX | Étiquettes: DUMAS, ENNIFAR, Unité ARN
@article{,
title = {Controlling Helix Formation in the γ-Peptide Superfamily: Heterogeneous Foldamers with Urea/Amide and Urea/Carbamate Backbones},
author = {N Pendem and Y R Nelli and C Douat and L Fischer and M Laguerre and E Ennifar and B Kauffmann and G Guichard},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23460200},
doi = {10.1002/anie.201209838},
isbn = {23460200},
year = {2013},
date = {2013-01-01},
journal = {Angew Chem Int Ed Engl},
volume = {52},
number = {15},
pages = {4147-51},
abstract = {One fold to rule them all: New heterogeneous aliphatic backbone foldamers belonging to the γ-peptide superfamily and containing various combinations of urea/amide (U/A) and urea/carbamate (U/C) units are reported. Structural studies at atomic resolution reveal hydrogen-bonded helical structures akin to that formed by cognate Un homooligomers.},
keywords = {DUMAS, ENNIFAR, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2011
Heppell B, Blouin S, Dussault A M, Mulhbacher J, Ennifar E, Penedo J C, Lafontaine D A
Molecular insights into the ligand-controlled organization of the SAM-I riboswitch Article de journal
Dans: Nat Chem Biol, vol. 7, no. 6, p. 384-92, 2011, ISBN: ISBN/1552-4469 (Electronic) 1552-4450 (Linking), (Published online 01 May 2011).
Résumé | Liens | BibTeX | Étiquettes: Aptamers, Bacterial/*chemistry *Riboswitch S-Adenosylmethionine/*chemistry, DUMAS, ENNIFAR, Nucleotide/chemistry Bacillus subtilis/genetics Binding Sites Crystallography, Unité ARN, X-Ray Ligands Metals Nucleic Acid Conformation RNA
@article{,
title = {Molecular insights into the ligand-controlled organization of the SAM-I riboswitch},
author = {B Heppell and S Blouin and A M Dussault and J Mulhbacher and E Ennifar and J C Penedo and D A Lafontaine},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21532599},
doi = {10.1038/nchembio.563},
isbn = {ISBN/1552-4469 (Electronic)
1552-4450 (Linking)},
year = {2011},
date = {2011-01-01},
journal = {Nat Chem Biol},
volume = {7},
number = {6},
pages = {384-92},
abstract = {S-adenosylmethionine (SAM) riboswitches are widespread in bacteria, and up to five different SAM riboswitch families have been reported, highlighting the relevance of SAM regulation. On the basis of crystallographic and biochemical data, it has been postulated, but never demonstrated, that ligand recognition by SAM riboswitches involves key conformational changes in the RNA architecture. We show here that the aptamer follows a two-step hierarchical folding selectively induced by metal ions and ligand binding, each of them leading to the formation of one of the two helical stacks observed in the crystal structure. Moreover, we find that the anti-antiterminator P1 stem is rotated along its helical axis upon ligand binding, a mechanistic feature that could be common to other riboswitches. We also show that the nonconserved P4 helical domain is used as an auxiliary element to enhance the ligand-binding affinity. This work provides the first comprehensive characterization, to our knowledge, of a ligand-controlled riboswitch folding pathway.},
note = {Published online 01 May 2011},
keywords = {Aptamers, Bacterial/*chemistry *Riboswitch S-Adenosylmethionine/*chemistry, DUMAS, ENNIFAR, Nucleotide/chemistry Bacillus subtilis/genetics Binding Sites Crystallography, Unité ARN, X-Ray Ligands Metals Nucleic Acid Conformation RNA},
pubstate = {published},
tppubtype = {article}
}
2010
Baussanne I, Bussiere A, Halder S, Ganem-Elbaz C, Ouberai M, Riou M, Paris J M, Ennifar E, Mingeot-Leclercq M P, Decout J L
Synthesis and antimicrobial evaluation of amphiphilic neamine derivatives Article de journal
Dans: J Med Chem, vol. 53, no. 1, p. 119-27, 2010, ISBN: 20000576, (1520-4804 (Electronic) 0022-2623 (Linking) Journal Article Research Support, Non-U.S. Gov't).
Résumé | Liens | BibTeX | Étiquettes: DUMAS, ENNIFAR, Unité ARN
@article{,
title = {Synthesis and antimicrobial evaluation of amphiphilic neamine derivatives},
author = {I Baussanne and A Bussiere and S Halder and C Ganem-Elbaz and M Ouberai and M Riou and J M Paris and E Ennifar and M P Mingeot-Leclercq and J L Decout},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20000576},
isbn = {20000576},
year = {2010},
date = {2010-01-01},
journal = {J Med Chem},
volume = {53},
number = {1},
pages = {119-27},
abstract = {The aminoglycoside antibiotics bind to the 16S bacterial rRNA and disturb the protein synthesis. One to four hydroxyl functions of the small aminoglycoside neamine were capped with phenyl, naphthyl, pyridyl, or quinolyl rings. The 3',4'- (6), 3',6- (7a), and the 3',4',6- (10a) 2-naphthylmethylene derivatives appeared to be active against sensitive and resistant Staphylococcus aureus strains. 10a also showed marked antibacterial activities against Gram (-) bacteria, including strains expressing enzymes modifying aminoglycosides, efflux pumps, or rRNA methylases. 7a and 10a revealed a weak and aspecific binding to a model bacterial 16S rRNA. Moreover, as compared to neomycin B, 10a showed a lower ability to decrease (3)H leucine incorporation into proteins in Pseudomonas aeruginosa. All together, our results suggest that the 3',4',6-tri-2-naphthylmethylene neamine derivative 10a should act against Gram (-) bacteria through a mechanism different from inhibition of protein synthesis, probably by membrane destabilization.},
note = {1520-4804 (Electronic)
0022-2623 (Linking)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {DUMAS, ENNIFAR, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Ennifar E, Walter P, Dumas P
Cation-dependent cleavage of the duplex form of the subtype-B HIV-1 RNA dimerization initiation site Article de journal
Dans: Nucleic Acids Res, vol. 38, no. 17, p. 5807-5811, 2010, ISBN: 20460458, (1362-4962 (Electronic) 0305-1048 (Linking) Journal article).
Résumé | Liens | BibTeX | Étiquettes: DUMAS, ENNIFAR, Unité ARN
@article{,
title = {Cation-dependent cleavage of the duplex form of the subtype-B HIV-1 RNA dimerization initiation site},
author = {E Ennifar and P Walter and P Dumas},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20460458},
isbn = {20460458},
year = {2010},
date = {2010-01-01},
journal = {Nucleic Acids Res},
volume = {38},
number = {17},
pages = {5807-5811},
abstract = {The crystal structure of subtype-B HIV-1 genomic RNA Dimerization Initiation Site duplex revealed chain cleavage at a specific position resulting in 3'-phosphate and 5'-hydroxyl termini. A crystallographic analysis showed that Ba(2+), Mn(2+), Co(2+) and Zn(2+) bind specifically on a guanine base close to the cleaved position. The crystal structures also point to a necessary conformational change to induce an 'in-line' geometry at the cleavage site. In solution, divalent cations increased the rate of cleavage with pH/pKa compensation, indicating that a cation-bound hydroxide anion is responsible for the cleavage. We propose a 'Trojan horse' mechanism, possibly of general interest, wherein a doubly charged cation hosted near the cleavage site as a 'harmless' species is further transformed in situ into an 'aggressive' species carrying a hydroxide anion.},
note = {1362-4962 (Electronic)
0305-1048 (Linking)
Journal article},
keywords = {DUMAS, ENNIFAR, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Fischer L, Claudon P, Pendem N, Miclet E, Didierjean C, Ennifar E, Guichard G
The canonical helix of urea oligomers at atomic resolution: insights into folding-induced axial organization Article de journal
Dans: Angew Chem Int Ed Engl, vol. 49, no. 6, p. 1067-70, 2010, ISBN: 20039243, (1521-3773 (Electronic) 1433-7851 (Linking) Journal Article Research Support, Non-U.S. Gov't).
Liens | BibTeX | Étiquettes: DUMAS, ENNIFAR, Unité ARN
@article{,
title = {The canonical helix of urea oligomers at atomic resolution: insights into folding-induced axial organization},
author = {L Fischer and P Claudon and N Pendem and E Miclet and C Didierjean and E Ennifar and G Guichard},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20039243},
isbn = {20039243},
year = {2010},
date = {2010-01-01},
journal = {Angew Chem Int Ed Engl},
volume = {49},
number = {6},
pages = {1067-70},
note = {1521-3773 (Electronic)
1433-7851 (Linking)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {DUMAS, ENNIFAR, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Freisz S, Bec G, Radi M, Wolff P, Crespan E, Angeli L, Dumas P, Maga G, Botta M, Ennifar E
Crystal structure of HIV-1 reverse transcriptase bound to a non-nucleoside inhibitor with a novel mechanism of action Article de journal
Dans: Angew Chem Int Ed Engl, vol. 49, no. 10, p. 1805-8, 2010, ISBN: 20135654, (1521-3773 (Electronic) 1433-7851 (Linking) Journal Article Research Support, Non-U.S. Gov't).
Liens | BibTeX | Étiquettes: 3-Ring/*chemistry Humans Indoles/*chemistry *Models, Anti-HIV Agents/*chemistry/therapeutic use Crystallography, Biological *Models, DUMAS, ENNIFAR, Molecular Molecular Structure Nitriles/*chemistry Pyridones/*chemistry Pyrimidines/*chemistry Reverse Transcriptase Inhibitors/*chemistry/therapeutic use Vinyl Compounds/*chemistry, Unité ARN, X-Ray HIV Protease Inhibitors/*chemistry/metabolism/pharmacology HIV Reverse Transcriptase/*chemistry/metabolism Heterocyclic Compounds
@article{,
title = {Crystal structure of HIV-1 reverse transcriptase bound to a non-nucleoside inhibitor with a novel mechanism of action},
author = {S Freisz and G Bec and M Radi and P Wolff and E Crespan and L Angeli and P Dumas and G Maga and M Botta and E Ennifar},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=20135654},
isbn = {20135654},
year = {2010},
date = {2010-01-01},
journal = {Angew Chem Int Ed Engl},
volume = {49},
number = {10},
pages = {1805-8},
note = {1521-3773 (Electronic)
1433-7851 (Linking)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {3-Ring/*chemistry Humans Indoles/*chemistry *Models, Anti-HIV Agents/*chemistry/therapeutic use Crystallography, Biological *Models, DUMAS, ENNIFAR, Molecular Molecular Structure Nitriles/*chemistry Pyridones/*chemistry Pyrimidines/*chemistry Reverse Transcriptase Inhibitors/*chemistry/therapeutic use Vinyl Compounds/*chemistry, Unité ARN, X-Ray HIV Protease Inhibitors/*chemistry/metabolism/pharmacology HIV Reverse Transcriptase/*chemistry/metabolism Heterocyclic Compounds},
pubstate = {published},
tppubtype = {article}
}
Sato Y, Ramalanjaona N, Huet T, Potier N, Osz J, Antony P, Peluso-Iltis C, Poussin-Courmontagne P, Ennifar E, Mely Y, Dejaegere A, Moras D, Rochel N
The "Phantom Effect" of the Rexinoid LG100754: structural and functional insights Article de journal
Dans: PLoS One, vol. 5, no. 11, p. e15119, 2010, ISBN: ISBN/1932-6203 (Electronic) 1932-6203 (Linking).
Résumé | Liens | BibTeX | Étiquettes: Animals Binding Sites Binding, Competitive Fluorescence Polarization Humans Ligands Mice Models, DUMAS, ENNIFAR, Molecular Protein Binding Protein Multimerization Protein Structure, Retinoic Acid/*chemistry/genetics/metabolism Recombinant Proteins/chemistry/metabolism Retinoid X Receptors/*chemistry/genetics/metabolism Retinoids/*chemistry/metabolism Scattering, Small Angle Tetrahydronaphthalenes/*chemistry/metabolism Tretinoin/*chemistry/metabolism X-Ray Diffraction, Tertiary Receptor Cross-Talk Receptors, Unité ARN
@article{,
title = {The "Phantom Effect" of the Rexinoid LG100754: structural and functional insights},
author = {Y Sato and N Ramalanjaona and T Huet and N Potier and J Osz and P Antony and C Peluso-Iltis and P Poussin-Courmontagne and E Ennifar and Y Mely and A Dejaegere and D Moras and N Rochel},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21152046},
doi = {10.1371/journal.pone.0015119},
isbn = {ISBN/1932-6203 (Electronic)
1932-6203 (Linking)},
year = {2010},
date = {2010-01-01},
journal = {PLoS One},
volume = {5},
number = {11},
pages = {e15119},
abstract = {Retinoic acid receptors (RARs) and Retinoid X nuclear receptors (RXRs) are ligand-dependent transcriptional modulators that execute their biological action through the generation of functional heterodimers. RXR acts as an obligate dimer partner in many signalling pathways, gene regulation by rexinoids depending on the liganded state of the specific heterodimeric partner. To address the question of the effect of rexinoid antagonists on RAR/RXR function, we solved the crystal structure of the heterodimer formed by the ligand binding domain (LBD) of the RARalpha bound to its natural agonist ligand (all-trans retinoic acid, atRA) and RXRalpha bound to a rexinoid antagonist (LG100754). We observed that RARalpha exhibits the canonical agonist conformation and RXRalpha an antagonist one with the C-terminal H12 flipping out to the solvent. Examination of the protein-LG100754 interactions reveals that its propoxy group sterically prevents the H12 associating with the LBD, without affecting the dimerization or the active conformation of RAR. Although LG100754 has been reported to act as a 'phantom ligand' activating RAR in a cellular context, our structural data and biochemical assays demonstrate that LG100754 mediates its effect as a full RXR antagonist. Finally we show that the 'phantom ligand effect' of the LG100754 is due to a direct binding of the ligand to RAR that stabilizes coactivator interactions thus accounting for the observed transcriptional activation of RAR/RXR.},
keywords = {Animals Binding Sites Binding, Competitive Fluorescence Polarization Humans Ligands Mice Models, DUMAS, ENNIFAR, Molecular Protein Binding Protein Multimerization Protein Structure, Retinoic Acid/*chemistry/genetics/metabolism Recombinant Proteins/chemistry/metabolism Retinoid X Receptors/*chemistry/genetics/metabolism Retinoids/*chemistry/metabolism Scattering, Small Angle Tetrahydronaphthalenes/*chemistry/metabolism Tretinoin/*chemistry/metabolism X-Ray Diffraction, Tertiary Receptor Cross-Talk Receptors, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2009
Burnouf D. Y., Wagner J. E.
Kinetics of deoxy-CTP incorporation opposite a dG-C8-N-2-aminofluorene adduct by a high-fidelity DNA polymerase Article de journal
Dans: J Mol Biol, vol. 386, no. 4, p. 951-61, 2009, (1089-8638 (Electronic) Journal Article Research Support, Non-U.S. Gov't).
Résumé | BibTeX | Étiquettes: Adducts, Bacillus, Catalytic, Cytidine, Deoxyguanosine/*metabolism, DNA, DNA-Directed, Domain, DUMAS, Elements, Fluorenes/*metabolism, Guanine, Kinetics, Oligonucleotides/metabolism, Phosphorothioate, Polymerase/*metabolism, Specificity, stearothermophilus/enzymology, Substrate, Titrimetry, Triphosphate/*metabolism
@article{,
title = {Kinetics of deoxy-CTP incorporation opposite a dG-C8-N-2-aminofluorene adduct by a high-fidelity DNA polymerase},
author = { D. Y. Burnouf and J. E. Wagner},
year = {2009},
date = {2009-01-01},
journal = {J Mol Biol},
volume = {386},
number = {4},
pages = {951-61},
abstract = {The model carcinogen N-2-acetylaminofluorene covalently binds to the C8 position of guanine to form two adducts, the N-(2'-deoxyguanosine-8-yl)-aminofluorene (G-AF) and the N-2-(2'-deoxyguanosine-8-yl)-acetylaminofluorene (G-AAF). Although they are chemically closely related, their biological effects are strongly different and they are processed by different damage tolerance pathways. G-AF is bypassed by replicative and high-fidelity polymerases, while specialized polymerases ensure synthesis past of G-AAF. We used the DNA polymerase I fragment of a Bacillus stearothermophilus strain as a model for a high-fidelity polymerase to study the kinetics of incorporation of deoxy-CTP (dCTP) opposite a single G-AF. Pre-steady-state kinetic experiments revealed a drastic reduction in dCTP incorporation performed by the G-AF-modified ternary complex. Two populations of these ternary complexes were identified: (i) a minor productive fraction (20%) that readily incorporates dCTP opposite the G-AF adduct with a rate similar to that measured for the adduct-free ternary complexes and (ii) a major fraction of unproductive complexes (80%) that slowly evolve into productive ones. In the light of structural data, we suggest that this slow rate reflects the translocation of the modified base within the active site, from the pre-insertion site into the insertion site. By making this translocation rate limiting, the G-AF lesion reveals a novel kinetic step occurring after dNTP binding and before chemistry.},
note = {1089-8638 (Electronic)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {Adducts, Bacillus, Catalytic, Cytidine, Deoxyguanosine/*metabolism, DNA, DNA-Directed, Domain, DUMAS, Elements, Fluorenes/*metabolism, Guanine, Kinetics, Oligonucleotides/metabolism, Phosphorothioate, Polymerase/*metabolism, Specificity, stearothermophilus/enzymology, Substrate, Titrimetry, Triphosphate/*metabolism},
pubstate = {published},
tppubtype = {article}
}
Wagner J., Etienne H., Fuchs R. P., Cordonnier A., Burnouf D.
Distinct beta-clamp interactions govern the activities of the Y family PolIV DNA polymerase Article de journal
Dans: Mol Microbiol, vol. 74, no. 5, p. 1143-51, 2009, (1365-2958 (Electronic) 0950-382X (Linking) Journal Article).
Résumé | BibTeX | Étiquettes: DUMAS
@article{,
title = {Distinct beta-clamp interactions govern the activities of the Y family PolIV DNA polymerase},
author = { J. Wagner and H. Etienne and R. P. Fuchs and A. Cordonnier and D. Burnouf},
year = {2009},
date = {2009-01-01},
journal = {Mol Microbiol},
volume = {74},
number = {5},
pages = {1143-51},
abstract = {The prototypic Y family DNA polymerase IV (PolIV) of Escherichia coli is involved in multiple replication-associated processes including spontaneous mutagenesis, translesion synthesis (TLS), cell fitness, survival under stressful conditions and checkpoint like functions. It interacts physically and functionally with the replisome's beta processivity clamp through the canonical PolIV C-terminal peptide (CTP). A second interaction that involves a portion of the little finger (LF) domain of PolIV has been structurally described. Here we show that the LF-beta interaction stabilizes the clamp-polymerase complex in vitro and is necessary for the access of PolIV to ongoing replication forks in vivo. However, in contrast to the CTP-beta, the LF-beta interaction is dispensable for the role of the polymerase in TLS. This discloses two independent modes of action for PolIV and, in turn, uncovers a novel way by which the cell may regulate the potentially deleterious effect of such low fidelity polymerases during replication.},
note = {1365-2958 (Electronic)
0950-382X (Linking)
Journal Article},
keywords = {DUMAS},
pubstate = {published},
tppubtype = {article}
}
Wagner J, Etienne H, Fuchs R P, Cordonnier A, Burnouf D
Distinct beta-clamp interactions govern the activities of the Y family PolIV DNA polymerase Article de journal
Dans: Mol Microbiol, vol. 74, no. 5, p. 1143-1151, 2009, ISBN: 19843218, (1365-2958 (Electronic) 0950-382X (Linking) Journal Article).
Résumé | Liens | BibTeX | Étiquettes: DUMAS, ENNIFAR, Unité ARN
@article{,
title = {Distinct beta-clamp interactions govern the activities of the Y family PolIV DNA polymerase},
author = {J Wagner and H Etienne and R P Fuchs and A Cordonnier and D Burnouf},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19843218},
isbn = {19843218},
year = {2009},
date = {2009-01-01},
journal = {Mol Microbiol},
volume = {74},
number = {5},
pages = {1143-1151},
abstract = {The prototypic Y family DNA polymerase IV (PolIV) of Escherichia coli is involved in multiple replication-associated processes including spontaneous mutagenesis, translesion synthesis (TLS), cell fitness, survival under stressful conditions and checkpoint like functions. It interacts physically and functionally with the replisome's beta processivity clamp through the canonical PolIV C-terminal peptide (CTP). A second interaction that involves a portion of the little finger (LF) domain of PolIV has been structurally described. Here we show that the LF-beta interaction stabilizes the clamp-polymerase complex in vitro and is necessary for the access of PolIV to ongoing replication forks in vivo. However, in contrast to the CTP-beta, the LF-beta interaction is dispensable for the role of the polymerase in TLS. This discloses two independent modes of action for PolIV and, in turn, uncovers a novel way by which the cell may regulate the potentially deleterious effect of such low fidelity polymerases during replication.},
note = {1365-2958 (Electronic)
0950-382X (Linking)
Journal Article},
keywords = {DUMAS, ENNIFAR, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Radi M, Maga G, Alongi M, Angeli L, Samuele A, Zanoli S, Bellucci L, Tafi A, Casaluce G, Giorgi G, Armand-Ugon M, Gonzalez E, Este J A, Baltzinger M, Bec G, Dumas P, Ennifar E, Botta M
Dans: J Med Chem, vol. 52, no. 3, p. 840-851, 2009, ISBN: 19140683, (1520-4804 (Electronic) Journal Article Research Support, Non-U.S. Gov't).
Résumé | Liens | BibTeX | Étiquettes: DUMAS, ENNIFAR, Unité ARN
@article{,
title = {Discovery of chiral cyclopropyl dihydro-alkylthio-benzyl-oxopyrimidine (S-DABO) derivatives as potent HIV-1 reverse transcriptase inhibitors with high activity against clinically relevant mutants},
author = {M Radi and G Maga and M Alongi and L Angeli and A Samuele and S Zanoli and L Bellucci and A Tafi and G Casaluce and G Giorgi and M Armand-Ugon and E Gonzalez and J A Este and M Baltzinger and G Bec and P Dumas and E Ennifar and M Botta},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19140683},
isbn = {19140683},
year = {2009},
date = {2009-01-01},
journal = {J Med Chem},
volume = {52},
number = {3},
pages = {840-851},
abstract = {The role played by stereochemistry in the C2-substituent (left part) on the S-DABO scaffold for anti-HIV-1 activity has been investigated for the first time. A series of S-DABO analogues, where the double bond in the C2-substituent is replaced by an enantiopure isosteric cyclopropyl moiety, has been synthesized, leading to the identification of a potent lead compound endowed with picomolar activity against RT (wt) and nanomolar activity against selected drug-resistant mutants. Molecular modeling calculation, enzymatic studies, and surface plasmon resonance experiments allowed us to rationalize the biological behavior of the synthesized compounds, which act as mixed-type inhibitors of HIV-1 RT K103N, with a preferential association to the enzyme-substrate complex. Taken together, our data show that the right combination of stereochemistry on the left and right parts (C6-substituent) of the S-DABO scaffold plays a key role in the inhibition of both wild-type and drug-resistant enzymes, especially the K103N mutant.},
note = {1520-4804 (Electronic)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {DUMAS, ENNIFAR, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2007
Ali M B, Chaminade F, Kanevsky I, Ennifar E, Josset L, Ficheux D, Darlix J L, Fosse P
Structural requirements for nucleocapsid protein-mediated dimerization of avian leukosis virus RNA Article de journal
Dans: J Mol Biol, vol. 372, no. 4, p. 1082-96, 2007, ISBN: 17706668.
Résumé | Liens | BibTeX | Étiquettes: DUMAS, ENNIFAR, Unité ARN
@article{,
title = {Structural requirements for nucleocapsid protein-mediated dimerization of avian leukosis virus RNA},
author = {M B Ali and F Chaminade and I Kanevsky and E Ennifar and L Josset and D Ficheux and J L Darlix and P Fosse},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17706668},
isbn = {17706668},
year = {2007},
date = {2007-01-01},
journal = {J Mol Biol},
volume = {372},
number = {4},
pages = {1082-96},
abstract = {The avian leukosis virus (ALV) belongs to the alpha group of retroviruses that are widespread in nature. The 5'-untranslated region of ALV genome contains the L3 element that is important for virus infectivity and the formation of an unstable RNA dimer in vitro. The L3 sequence is predicted to fold into a long stem-loop structure with two internal loops and an apical one. Phylogenetic analysis predicts that the L3 stem-loop is conserved in alpharetroviruses. Furthermore, a significant selection mechanism maintains a palindrome in the apical loop. The nucleocapsid protein of the alpharetroviruses (NCp12) is required for RNA dimer formation and replication in vivo. It is not known whether L3 can be an NCp12-mediated RNA dimerization site able to bind NCp12 with high affinity. Here, we report that NCp12 chaperones formation of a stable ALV RNA dimer through L3. To investigate the NCp12-mediated L3 dimerization reaction, we performed site-directed mutagenesis, gel retardation and heterodimerization assays and analysis of thermostability of dimeric RNAs. We show that the affinity of NCp12 for L3 is lower than its affinity for the microPsi RNA packaging signal. Results show that conservation of a long stem-loop structure and a loop-loop interaction are not required for NCp12-mediated L3 dimerization. We show that the L3 apical stem-loop is sufficient to form an extended duplex and the whole stem-loop L3 cannot be converted by NCp12 into a duplex extending throughout L3. Three-dimensional modelling of the stable L3 dimer supports the notion that the extended duplex may represent the minimal dimer linkage structure found in the genomic RNA.},
keywords = {DUMAS, ENNIFAR, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Bernacchi S, Freisz S, Maechling C, Spiess B, Marquet R, Dumas P, Ennifar E
Aminoglycoside binding to the HIV-1 RNA dimerization initiation site: thermodynamics and effect on the kissing-loop to duplex conversion Article de journal
Dans: Nucleic Acids Res, vol. 35, no. 21, p. 7128-39, 2007, ISBN: 17942426, (1362-4962 (Electronic)).
Résumé | Liens | BibTeX | Étiquettes: DUMAS, ENNIFAR, MARQUET, Unité ARN
@article{,
title = {Aminoglycoside binding to the HIV-1 RNA dimerization initiation site: thermodynamics and effect on the kissing-loop to duplex conversion},
author = {S Bernacchi and S Freisz and C Maechling and B Spiess and R Marquet and P Dumas and E Ennifar},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17942426},
isbn = {17942426},
year = {2007},
date = {2007-01-01},
journal = {Nucleic Acids Res},
volume = {35},
number = {21},
pages = {7128-39},
abstract = {Owing to a striking, and most likely fortuitous, structural and sequence similarity with the bacterial 16 S ribosomal A site, the RNA kissing-loop complex formed by the HIV-1 genomic RNA dimerization initiation site (DIS) specifically binds 4,5-disubstituted 2-deoxystreptamine (2-DOS) aminoglycoside antibiotics. We used chemical probing, molecular modeling, isothermal titration calorimetry (ITC) and UV melting to investigate aminoglycoside binding to the DIS loop-loop complex. We showed that apramycin, an aminoglycoside containing a bicyclic moiety, also binds the DIS, but in a different way than 4,5-disubstituted 2-DOS aminoglycosides. The determination of thermodynamic parameters for various aminoglycosides revealed the role of the different rings in the drug-RNA interaction. Surprisingly, we found that the affinity of lividomycin and neomycin for the DIS (K(d) approximately 30 nM) is significantly higher than that obtained in the same experimental conditions for their natural target, the bacterial A site (K(d) approximately 1.6 microM). In good agreement with their respective affinity, aminoglycoside increase the melting temperature of the loop-loop interaction and also block the conversion from kissing-loop complex to extended duplex. Taken together, our data might be useful for selecting new molecules with improved specificity and affinity toward the HIV-1 DIS RNA.},
note = {1362-4962 (Electronic)},
keywords = {DUMAS, ENNIFAR, MARQUET, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Olieric V, Ennifar E, Meents A, Fleurant M, Besnard C, Pattison P, Schiltz M, Schulze-Briese C, Dumas P
Using X-ray absorption spectra to monitor specific radiation damage to anomalously scattering atoms in macromolecular crystallography Article de journal
Dans: Acta Crystallogr D Biol Crystallogr, vol. 63, no. Pt 7, p. 759-68, 2007, ISBN: 17582167.
Résumé | Liens | BibTeX | Étiquettes: DUMAS, ENNIFAR, Unité ARN
@article{,
title = {Using X-ray absorption spectra to monitor specific radiation damage to anomalously scattering atoms in macromolecular crystallography},
author = {V Olieric and E Ennifar and A Meents and M Fleurant and C Besnard and P Pattison and M Schiltz and C Schulze-Briese and P Dumas},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17582167},
isbn = {17582167},
year = {2007},
date = {2007-01-01},
journal = {Acta Crystallogr D Biol Crystallogr},
volume = {63},
number = {Pt 7},
pages = {759-68},
abstract = {Radiation damage in macromolecular crystals is not suppressed even at 90 K. This is particularly true for covalent bonds involving an anomalous scatterer (such as bromine) at the 'peak wavelength'. It is shown that a series of absorption spectra recorded on a brominated RNA faithfully monitor the extent of cleavage. The continuous spectral changes during irradiation preserve an 'isosbestic point', each spectrum being a linear combination of 'zero' and 'infinite' dose spectra. This easily yields a good estimate of the partial occupancy of bromine at any intermediate dose. The considerable effect on the near-edge features in the spectra of the crystal orientation versus the beam polarization has also been examined and found to be in good agreement with a previous study. Any significant influence of the (C-Br bond/beam polarization) angle on the cleavage kinetics of bromine was also searched for, but was not detected. These results will be useful for standard SAD/MAD experiments and for the emerging 'radiation-damage-induced phasing' method exploiting both the anomalous signal of an anomalous scatterer and the 'isomorphous' signal resulting from its cleavage.},
keywords = {DUMAS, ENNIFAR, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Reblova K, Fadrna E, Sarzynska J, Kulinski T, Kulhanek P, Ennifar E, Koca J, Sponer J
Conformations of Flanking Bases in HIV-1 RNA DIS Kissing Complexes Studied by Molecular Dynamics Article de journal
Dans: Biophys J, vol. 93, no. 11, p. 3932-3949, 2007, ISBN: 17704156, (0006-3495 (Print) Journal article).
Résumé | Liens | BibTeX | Étiquettes: DUMAS, ENNIFAR, Unité ARN
@article{,
title = {Conformations of Flanking Bases in HIV-1 RNA DIS Kissing Complexes Studied by Molecular Dynamics},
author = {K Reblova and E Fadrna and J Sarzynska and T Kulinski and P Kulhanek and E Ennifar and J Koca and J Sponer},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17704156},
isbn = {17704156},
year = {2007},
date = {2007-01-01},
journal = {Biophys J},
volume = {93},
number = {11},
pages = {3932-3949},
abstract = {Explicit solvent molecular dynamics simulations (in total almost 800 ns including locally enhanced sampling runs) were applied with different ion conditions and with two force fields (AMBER and CHARMM) to characterize typical geometries adopted by the flanking bases in the RNA kissing-loop complexes. We focus on flanking base positions in multiple x-ray and NMR structures of HIV-1 DIS kissing complexes and kissing complex from the large ribosomal subunit of Haloarcula marismortui. An initial x-ray open conformation of bulged-out bases in HIV-1 DIS complexes, affected by crystal packing, tends to convert to a closed conformation formed by consecutive stretch of four stacked purine bases. This is in agreement with those recent crystals where the packing is essentially avoided. We also observed variants of the closed conformation with three stacked bases, while nonnegligible populations of stacked geometries with bulged-in bases were detected, too. The simulation results reconcile differences in positions of the flanking bases observed in x-ray and NMR studies. Our results suggest that bulged-out geometries are somewhat more preferred, which is in accord with recent experiments showing that they may mediate tertiary contacts in biomolecular assemblies or allow binding of aminoglycoside antibiotics.},
note = {0006-3495 (Print)
Journal article},
keywords = {DUMAS, ENNIFAR, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2006
Ambert N., Vanwinsberghe J., Dumas P.
Biocrystallographica, a package for doing crystallography with Mathematica Divers
2006.
@misc{,
title = {Biocrystallographica, a package for doing crystallography with Mathematica},
author = { N. Ambert and J. Vanwinsberghe and P. Dumas},
year = {2006},
date = {2006-01-01},
volume = {2006},
publisher = {IUCR},
keywords = {DUMAS},
pubstate = {published},
tppubtype = {misc}
}
Dumas P., Vanwinsberghe J., Cura V.
Einstein's tongue for teaching crystallography to biologists Divers
2006.
@misc{,
title = {Einstein's tongue for teaching crystallography to biologists},
author = { P. Dumas and J. Vanwinsberghe and V. Cura},
year = {2006},
date = {2006-01-01},
volume = {2006},
publisher = {IUCR},
keywords = {DUMAS},
pubstate = {published},
tppubtype = {misc}
}
Ambert N, Vanwinsberghe J, Dumas P
Biocrystallographica, a package for doing crystallography with Mathematica Divers
2006.
@misc{,
title = {Biocrystallographica, a package for doing crystallography with Mathematica},
author = {N Ambert and J Vanwinsberghe and P Dumas},
year = {2006},
date = {2006-01-01},
volume = {2006},
publisher = {IUCR},
keywords = {DUMAS},
pubstate = {published},
tppubtype = {misc}
}
Dumas P, Vanwinsberghe J, Cura V
Einstein's tongue for teaching crystallography to biologists Divers
2006.
@misc{,
title = {Einstein's tongue for teaching crystallography to biologists},
author = {P Dumas and J Vanwinsberghe and V Cura},
year = {2006},
date = {2006-01-01},
volume = {2006},
publisher = {IUCR},
keywords = {DUMAS},
pubstate = {published},
tppubtype = {misc}
}
Ambert N, Vanwinsberghe J, Dumas P
Biocrystallographica, a package for doing crystallography with Mathematica Divers
2006.
@misc{,
title = {Biocrystallographica, a package for doing crystallography with Mathematica},
author = {N Ambert and J Vanwinsberghe and P Dumas},
year = {2006},
date = {2006-01-01},
volume = {2006},
publisher = {IUCR},
keywords = {DUMAS},
pubstate = {published},
tppubtype = {misc}
}
Dumas P, Vanwinsberghe J, Cura V
Einstein's tongue for teaching crystallography to biologists Divers
2006.
@misc{,
title = {Einstein's tongue for teaching crystallography to biologists},
author = {P Dumas and J Vanwinsberghe and V Cura},
year = {2006},
date = {2006-01-01},
volume = {2006},
publisher = {IUCR},
keywords = {DUMAS},
pubstate = {published},
tppubtype = {misc}
}
Ennifar E, Dumas P
Polymorphism of bulged-out residues in HIV-1 RNA DIS kissing complex and structure comparison with solution studies Article de journal
Dans: J Mol Biol, vol. 356, no. 3, p. 771-782, 2006, ISBN: 16403527, (0022-2836 (Print) Journal Article).
Résumé | Liens | BibTeX | Étiquettes: DUMAS, ENNIFAR, Unité ARN
@article{,
title = {Polymorphism of bulged-out residues in HIV-1 RNA DIS kissing complex and structure comparison with solution studies},
author = {E Ennifar and P Dumas},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16403527},
isbn = {16403527},
year = {2006},
date = {2006-01-01},
journal = {J Mol Biol},
volume = {356},
number = {3},
pages = {771-782},
abstract = {All retroviruses encapsidate their genome as a dimer of homologous single-stranded RNAs. The dimerization initiation site (DIS) of human immunodeficiency virus type 1 (HIV-1) is located in the 5'-untranslated region of the viral genome and consists of a hairpin with a 6 nt self-complementary loop sequence. Genomic RNA dimerization, a crucial step for virion infectivity, is promoted by the formation of a loop-loop complex (or kissing complex) between two DIS hairpins. Crystal structures for the subtypes A, B and F of the HIV-1 DIS kissing complex have now been solved at 2.3 A, 1.9 A and 1.6 A, respectively. They revealed a polymorphism of bulged-out residues showing clearly that their conformation is not a mere consequence of crystal packing. They also provide more insights into ion binding, hydration, and RNA conformation and flexibility. In particular, we observed the binding of spermine to the loop-loop helix, which displaced a magnesium cation important for subtype A DIS dimerization. The excellent agreement between X-ray structures and the results of chemical probing and interference data on larger viral RNA fragments shows that the crystal structures are relevant for the DIS kissing complex present in solution and in viral particles. Accordingly, these structures will be helpful for designing new drugs derived from aminoglycoside antibiotics and targeted against the RNA dimerization step of the viral life-cycle.},
note = {0022-2836 (Print)
Journal Article},
keywords = {DUMAS, ENNIFAR, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Dumas P, Vanwinsberghe J, Cura V
Einstein's tongue for teaching crystallography to biologists Divers
2006.
BibTeX | Étiquettes: DUMAS, Unité ARN
@misc{,
title = {Einstein's tongue for teaching crystallography to biologists},
author = {P Dumas and J Vanwinsberghe and V Cura},
year = {2006},
date = {2006-01-01},
volume = {2006},
publisher = {IUCR},
keywords = {DUMAS, Unité ARN},
pubstate = {published},
tppubtype = {misc}
}
Ambert N, Vanwinsberghe J, Dumas P
Biocrystallographica, a package for doing crystallography with Mathematica Divers
2006.
BibTeX | Étiquettes: DUMAS, Unité ARN
@misc{,
title = {Biocrystallographica, a package for doing crystallography with Mathematica},
author = {N Ambert and J Vanwinsberghe and P Dumas},
year = {2006},
date = {2006-01-01},
volume = {2006},
publisher = {IUCR},
keywords = {DUMAS, Unité ARN},
pubstate = {published},
tppubtype = {misc}
}
2005
Ennifar E, Basquin J, Birkenbihl R, Suck D
Purification, crystallization and preliminary X-ray diffraction studies of the archaeal virus resolvase SIRV2 Article de journal
Dans: Acta Crystallogr F Struct Biol Commun, vol. 61, no. Pt 5, p. 507-509, 2005, ISBN: 16511081, (1744-3091 (Electronic) Journal Article).
Résumé | Liens | BibTeX | Étiquettes: DUMAS, ENNIFAR, Unité ARN
@article{,
title = {Purification, crystallization and preliminary X-ray diffraction studies of the archaeal virus resolvase SIRV2},
author = {E Ennifar and J Basquin and R Birkenbihl and D Suck},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16511081},
isbn = {16511081},
year = {2005},
date = {2005-01-01},
journal = {Acta Crystallogr F Struct Biol Commun},
volume = {61},
number = {Pt 5},
pages = {507-509},
abstract = {The Holliday junction (or four-way junction) is the universal DNA intermediate whose interaction with resolving proteins is one of the major events in the recombinational process. These proteins, called DNA junction-resolving enzymes or resolvases, bind to the junction and catalyse DNA cleavage, promoting the release of two DNA duplexes. SIRV2 Hjc, a viral resolvase infecting a thermophylic archaeon, has been cloned, expressed and purified. Crystals have been obtained in space group C2, with unit-cell parameters a = 147.8},
note = {1744-3091 (Electronic)
Journal Article},
keywords = {DUMAS, ENNIFAR, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
2004
Burnouf D. Y., Olieric V., Wagner J., Fujii S., Reinbolt J., Fuchs R. P., Dumas P.
Structural and biochemical analysis of sliding clamp/ligand interactions suggest a competition between replicative and translesion DNA polymerases Article de journal
Dans: J Mol Biol, vol. 335, no. 5, p. 1187-97, 2004, (0022-2836 Journal Article).
Résumé | BibTeX | Étiquettes: *Binding, Antigen/metabolism, Bacterial/genetics, beta/*chemistry/genetics/*metabolism, Binding, Cell, coli/*enzymology, Competitive, Crystallization, DNA, DUMAS, Escherichia, Fragments/*metabolism, I/metabolism, III/metabolism, Kinetics, ligands, Models, Molecular, Nuclear, Peptide, Polymerase, Proliferating, Protein, Proteins/chemistry/metabolism, Recombinant, Replication/*genetics, Subunits
@article{,
title = {Structural and biochemical analysis of sliding clamp/ligand interactions suggest a competition between replicative and translesion DNA polymerases},
author = { D. Y. Burnouf and V. Olieric and J. Wagner and S. Fujii and J. Reinbolt and R. P. Fuchs and P. Dumas},
year = {2004},
date = {2004-01-01},
journal = {J Mol Biol},
volume = {335},
number = {5},
pages = {1187-97},
abstract = {Most DNA polymerases interact with their cognate processive replication factor through a small peptide, this interaction being absolutely required for their function in vivo. We have solved the crystal structure of a complex between the beta sliding clamp of Escherichia coli and the 16 residue C-terminal peptide of Pol IV (P16). The seven C-terminal residues bind to a pocket located at the surface of one beta monomer. This region was previously identified as the binding site of another beta clamp binding protein, the delta subunit of the gamma complex. We show that peptide P16 competitively prevents beta-clamp-mediated stimulation of both Pol IV and alpha subunit DNA polymerase activities, suggesting that the site of interaction of the alpha subunit with beta is identical with, or overlaps that of Pol IV. This common binding site for delta, Pol IV and alpha subunit is shown to be formed by residues that are highly conserved among many bacterial beta homologs, thus defining an evolutionarily conserved hydrophobic crevice for sliding clamp ligands and a new target for antibiotic drug design.},
note = {0022-2836
Journal Article},
keywords = {*Binding, Antigen/metabolism, Bacterial/genetics, beta/*chemistry/genetics/*metabolism, Binding, Cell, coli/*enzymology, Competitive, Crystallization, DNA, DUMAS, Escherichia, Fragments/*metabolism, I/metabolism, III/metabolism, Kinetics, ligands, Models, Molecular, Nuclear, Peptide, Polymerase, Proliferating, Protein, Proteins/chemistry/metabolism, Recombinant, Replication/*genetics, Subunits},
pubstate = {published},
tppubtype = {article}
}
Delarue M., Dumas P.
On the use of low-frequency normal modes to enforce collective movements in refining macromolecular structural models Article de journal
Dans: Proc Natl Acad Sci U S A, vol. 101, no. 18, p. 6957-62, 2004, (0027-8424 Journal Article).
Résumé | BibTeX | Étiquettes: *Models, Carrier, coli, Computer, Diffraction, DUMAS, Escherichia, Gov't, Molecular, Non-U.S., Proteins/*chemistry, Proteins/chemistry, Simulation, Support, X-Ray
@article{,
title = {On the use of low-frequency normal modes to enforce collective movements in refining macromolecular structural models},
author = { M. Delarue and P. Dumas},
year = {2004},
date = {2004-01-01},
journal = {Proc Natl Acad Sci U S A},
volume = {101},
number = {18},
pages = {6957-62},
abstract = {As more and more structures of macromolecular complexes get solved in different conditions, it has become apparent that flexibility is an inherent part of their biological function. Normal mode analysis using simplified models of proteins such as the elastic network model has proved very effective in showing that many of the structural transitions derived from a survey of the Protein Data Bank can be explained by just a few of the lowest-frequency normal modes. In this work, normal modes are used to carry out medium- or low-resolution structural refinement, enforcing collective and large-amplitude movements that are beyond the reach of existing methods. Refinement is carried out in reciprocal space with respect to the normal mode amplitudes, by using standard conjugate-gradient minimization. Several tests on synthetic diffraction data whose mode concentration follows the one of real movements observed in the Protein Data Bank have shown that the radius of convergence is larger than the one of rigid-body refinement. Tests with experimental diffraction data for the same protein in different environments also led to refined structural models showing drastic reduction of the rms deviation with the target model. Because the structural transition is described by very few parameters, over-fitting of real experimental data is easily detected by using a cross-validation test. The method has also been applied to the refinement of atomic models into molecular envelopes and could readily be used to fit large macromolecular complex rearrangements into cryo-electron microscopy-reconstructed images as well as small-angle x-ray scattering-derived envelopes.},
note = {0027-8424
Journal Article},
keywords = {*Models, Carrier, coli, Computer, Diffraction, DUMAS, Escherichia, Gov't, Molecular, Non-U.S., Proteins/*chemistry, Proteins/chemistry, Simulation, Support, X-Ray},
pubstate = {published},
tppubtype = {article}
}
Schiltz M, Dumas P, Ennifar E, Flensburg C, Paciorek W, Vonrhein C, Bricogne G
Phasing in the presence of severe site-specific radiation damage through dose-dependent modelling of heavy atoms Article de journal
Dans: Acta Crystallogr D Biol Crystallogr, vol. 60, no. Pt 6, p. 1024-1031, 2004, ISBN: 15159561, (0907-4449 Journal Article).
Résumé | Liens | BibTeX | Étiquettes: DUMAS, ENNIFAR, Unité ARN
@article{,
title = {Phasing in the presence of severe site-specific radiation damage through dose-dependent modelling of heavy atoms},
author = {M Schiltz and P Dumas and E Ennifar and C Flensburg and W Paciorek and C Vonrhein and G Bricogne},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15159561},
isbn = {15159561},
year = {2004},
date = {2004-01-01},
journal = {Acta Crystallogr D Biol Crystallogr},
volume = {60},
number = {Pt 6},
pages = {1024-1031},
abstract = {The case of a brominated RNA crystal structure determination in which standard three-wavelength MAD phasing was unsuccessful because of fast X-ray-induced debromination was reinvestigated [Ennifar et al. (2002), Acta Cryst. D58, 1262-1268]. It was found that if the data are kept unmerged and if a dose-stamp is associated with each reflection measurement, dose-dependent occupancies can be refined for the Br atoms. Such a parametrization has been implemented in the macromolecular phasing program SHARP. Refining such dose-dependent occupancies on an unmerged data set gave a dramatic improvement, even for SAD phases from only the first wavelength (peak), and resulted in a good electron-density map after solvent flattening. The adverse effect of radiation damage has been turned into a beneficial one. The crucial difference is made by the use of unmerged data: phasing power is generated through the intensity differences of symmetry-related reflections recorded at different doses, i.e. corresponding to different states of the X-ray-induced debromination. This approach should prove useful in all situations of experimental phasing where site-specific radiation damage occurs unavoidably and undesirably and not only in cases in which radiation damage is purposely being created in order to demonstrate its potential usefulness.},
note = {0907-4449
Journal Article},
keywords = {DUMAS, ENNIFAR, Unité ARN},
pubstate = {published},
tppubtype = {article}
}
Ehresmann C, Ehresmann B, Ennifar E, Dumas P, Garber M, Mathy N, Nikulin A, Portier C, Patel D, Serganov A
Molecular mimicry in translational regulation: the case of ribosomal protein S15. Article de journal
Dans: RNA Biol, vol. 1, no. 1, p. 66-73, 2004, ISBN: 17194931, (Epub 2004 May 5.).
Résumé | Liens | BibTeX | Étiquettes: DUMAS, ENNIFAR, Unité ARN
@article{,
title = {Molecular mimicry in translational regulation: the case of ribosomal protein S15.},
author = {C Ehresmann and B Ehresmann and E Ennifar and P Dumas and M Garber and N Mathy and A Nikulin and C Portier and D Patel and A Serganov},
url = {http://www.ncbi.nlm.nih.gov/pubmed/17194931},
isbn = {17194931},
year = {2004},
date = {2004-01-01},
journal = {RNA Biol},
volume = {1},
number = {1},
pages = {66-73},
abstract = {Ribosomal protein S15 is highly conserved among prokaryotes. It plays a pivotal role in the assembly of the central domain of the small ribosomal subunit and regulates its own expression by a feedback mechanism at the translational level. The protein recognizes two RNA targets (rRNA and mRNA) that share only partial similarity. Its interaction with 16S rRNA has been fully characterized, while mRNA interactions and regulatory mechanisms have been extensively studied in E. coli and in T. thermophilus. Recently, we have characterized which aminoacids are involved in E. coli mRNA recognition, using an in vivo assay allowing to identify S15 mutations affecting the S15-mRNA interactions without altering 30S subunit assembly. Here, we address the following questions: Are common determinants used by S15 to recognize its rRNA and mRNA targets? What is the extent of molecular mimicry? Is the regulatory mechanism conserved? Our results indicate that specific recognition of mRNA and rRNA relies on both mimicry and site differentiation. They also highlight the high plasticity of RNA to adapt to evolutionary constraints.},
note = {Epub 2004 May 5.},
keywords = {DUMAS, ENNIFAR, Unité ARN},
pubstate = {published},
tppubtype = {article}
}