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I2CT
Immunologie, Immunopathologie et Chimie Thérapeutique
Publications
1999
Dumas P., Bergdoll M., Masson J.
Comments on the paper by kumagai, hibino, kawano and sugiyama (1999) FEBS lett. 450, 227-230 Article de journal
Dans: FEBS Lett, vol. 459, no. 2, p. 282-3;discussion 284, 1999, (0014-5793 Comment Journal Article).
BibTeX | Étiquettes: *Acetyltransferases, Antibiotics, Bacterial, Bleomycin/*metabolism/pharmacology, effects/genetics/*metabolism, Glycopeptide/metabolism/pharmacology, Mutation, Proline/*genetics/pharmacology, Proteins/genetics/*metabolism, Streptomyces/drug
@article{,
title = {Comments on the paper by kumagai, hibino, kawano and sugiyama (1999) FEBS lett. 450, 227-230},
author = { P. Dumas and M. Bergdoll and J. Masson},
year = {1999},
date = {1999-01-01},
journal = {FEBS Lett},
volume = {459},
number = {2},
pages = {282-3;discussion 284},
note = {0014-5793
Comment
Journal Article},
keywords = {*Acetyltransferases, Antibiotics, Bacterial, Bleomycin/*metabolism/pharmacology, effects/genetics/*metabolism, Glycopeptide/metabolism/pharmacology, Mutation, Proline/*genetics/pharmacology, Proteins/genetics/*metabolism, Streptomyces/drug},
pubstate = {published},
tppubtype = {article}
}
1998
Bergdoll M., Eltis L. D., Cameron A. D., Dumas P., Bolin J. T.
All in the family: structural and evolutionary relationships among three modular proteins with diverse functions and variable assembly Article de journal
Dans: Protein Sci, vol. 7, no. 8, p. 1661-70, 1998, (0961-8368 Journal Article).
Résumé | BibTeX | Étiquettes: *Acetyltransferases, *Evolution, Acid, Amino, Bacterial, Burkholderia/*chemistry, Crystallography, Data, Genetic, Gov't, Homology, Human, Lactoylglutathione, Lyase/*chemistry, Models, Molecular, Non-U.S., Oxygenases/chemistry, P.H.S., Phylogeny, Protein, Proteins/*chemistry, Secondary, Sequence, structure, Support, U.S., X-Ray
@article{,
title = {All in the family: structural and evolutionary relationships among three modular proteins with diverse functions and variable assembly},
author = { M. Bergdoll and L. D. Eltis and A. D. Cameron and P. Dumas and J. T. Bolin},
year = {1998},
date = {1998-01-01},
journal = {Protein Sci},
volume = {7},
number = {8},
pages = {1661-70},
abstract = {The crystal structures of three proteins of diverse function and low sequence similarity were analyzed to evaluate structural and evolutionary relationships. The proteins include a bacterial bleomycin resistance protein, a bacterial extradiol dioxygenase, and human glyoxalase I. Structural comparisons, as well as phylogenetic analyses, strongly indicate that the modern family of proteins represented by these structures arose through a rich evolutionary history that includes multiple gene duplication and fusion events. These events appear to be historically shared in some cases, but parallel and historically independent in others. A significant early event is proposed to be the establishment of metal-binding in an oligomeric ancestor prior to the first gene fusion. Variations in the spatial arrangements of homologous modules are observed that are consistent with the structural principles of three-dimensional domain swapping, but in the unusual context of the formation of larger monomers from smaller dimers or tetramers. The comparisons support a general mechanism for metalloprotein evolution that exploits the symmetry of a homooligomeric protein to originate a metal binding site and relies upon the relaxation of symmetry, as enabled by gene duplication, to establish and refine specific functions.},
note = {0961-8368
Journal Article},
keywords = {*Acetyltransferases, *Evolution, Acid, Amino, Bacterial, Burkholderia/*chemistry, Crystallography, Data, Genetic, Gov't, Homology, Human, Lactoylglutathione, Lyase/*chemistry, Models, Molecular, Non-U.S., Oxygenases/chemistry, P.H.S., Phylogeny, Protein, Proteins/*chemistry, Secondary, Sequence, structure, Support, U.S., X-Ray},
pubstate = {published},
tppubtype = {article}
}
The crystal structures of three proteins of diverse function and low sequence similarity were analyzed to evaluate structural and evolutionary relationships. The proteins include a bacterial bleomycin resistance protein, a bacterial extradiol dioxygenase, and human glyoxalase I. Structural comparisons, as well as phylogenetic analyses, strongly indicate that the modern family of proteins represented by these structures arose through a rich evolutionary history that includes multiple gene duplication and fusion events. These events appear to be historically shared in some cases, but parallel and historically independent in others. A significant early event is proposed to be the establishment of metal-binding in an oligomeric ancestor prior to the first gene fusion. Variations in the spatial arrangements of homologous modules are observed that are consistent with the structural principles of three-dimensional domain swapping, but in the unusual context of the formation of larger monomers from smaller dimers or tetramers. The comparisons support a general mechanism for metalloprotein evolution that exploits the symmetry of a homooligomeric protein to originate a metal binding site and relies upon the relaxation of symmetry, as enabled by gene duplication, to establish and refine specific functions.
1997
Bergdoll M., Remy M. H., Cagnon C., Masson J. M., Dumas P.
Proline-dependent oligomerization with arm exchange Article de journal
Dans: Structure, vol. 5, no. 3, p. 391-401, 1997, (0969-2126 Journal Article).
Résumé | BibTeX | Étiquettes: *Acetyltransferases, *Dimerization, *Protein, Acid, Alignment, Amino, Aminotransferases/chemistry, Animals, Aspartate, ATPase/chemistry, Bacterial, Binding, Cattle, Chickens, Comparative, Conformation, Data, Folding, Heart/enzymology, Human, mitochondria, Models, Molecular, Mutagenesis, Na(+)-K(+)-Exchanging, Pancreatic/chemistry, Plant, Proline/*physiology, Protein, Proteins/chemistry, Pyrophosphatases/chemistry, Ribonuclease, Sequence, Site-Directed, Structural, Study, Viral, Viruses/chemistry
@article{,
title = {Proline-dependent oligomerization with arm exchange},
author = { M. Bergdoll and M. H. Remy and C. Cagnon and J. M. Masson and P. Dumas},
year = {1997},
date = {1997-01-01},
journal = {Structure},
volume = {5},
number = {3},
pages = {391-401},
abstract = {BACKGROUND: Oligomerization is often necessary for protein activity or regulation and its efficiency is fundamental for the cell. The quaternary structure of a large number of oligomers consists of protomers tightly anchored to each other by exchanged arms or swapped domains. However, nothing is known about how the arms can be kept in a favourable conformation before such an oligomerization. RESULTS: Upon examination of such quaternary structures, we observe an extremely frequent occurrence of proline residues at the point where the arm leaves the protomer. Sequence alignment and site-directed mutagenesis confirm the importance of these prolines. The conservation of these residues at the hinge regions can be explained by the constraints that they impose on polypeptide conformation and dynamics: by rigidifying the mainchain, prolines favour extended conformations of arms thus favouring oligomerization, and may prevent interaction of the arms with the core of the protomer. CONCLUSIONS: Hinge prolines can be considered as 'quaternary structure helpers'. The presence of a proline should be considered when searching for a determinant of oligomerization with arm exchange and could be used to engineer synthetic oligomers or to displace a monomers to oligomers equilibrium by mutation of this proline residue.},
note = {0969-2126
Journal Article},
keywords = {*Acetyltransferases, *Dimerization, *Protein, Acid, Alignment, Amino, Aminotransferases/chemistry, Animals, Aspartate, ATPase/chemistry, Bacterial, Binding, Cattle, Chickens, Comparative, Conformation, Data, Folding, Heart/enzymology, Human, mitochondria, Models, Molecular, Mutagenesis, Na(+)-K(+)-Exchanging, Pancreatic/chemistry, Plant, Proline/*physiology, Protein, Proteins/chemistry, Pyrophosphatases/chemistry, Ribonuclease, Sequence, Site-Directed, Structural, Study, Viral, Viruses/chemistry},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Oligomerization is often necessary for protein activity or regulation and its efficiency is fundamental for the cell. The quaternary structure of a large number of oligomers consists of protomers tightly anchored to each other by exchanged arms or swapped domains. However, nothing is known about how the arms can be kept in a favourable conformation before such an oligomerization. RESULTS: Upon examination of such quaternary structures, we observe an extremely frequent occurrence of proline residues at the point where the arm leaves the protomer. Sequence alignment and site-directed mutagenesis confirm the importance of these prolines. The conservation of these residues at the hinge regions can be explained by the constraints that they impose on polypeptide conformation and dynamics: by rigidifying the mainchain, prolines favour extended conformations of arms thus favouring oligomerization, and may prevent interaction of the arms with the core of the protomer. CONCLUSIONS: Hinge prolines can be considered as 'quaternary structure helpers'. The presence of a proline should be considered when searching for a determinant of oligomerization with arm exchange and could be used to engineer synthetic oligomers or to displace a monomers to oligomers equilibrium by mutation of this proline residue.
1994
Dumas P., Bergdoll M., Cagnon C., Masson J. M.
Crystal structure and site-directed mutagenesis of a bleomycin resistance protein and their significance for drug sequestering Article de journal
Dans: EMBO J, vol. 13, no. 11, p. 2483-92, 1994, (0261-4189 Journal Article).
Résumé | BibTeX | Étiquettes: *Acetyltransferases, &, Acid, Amino, Bacterial, Bacterial/*genetics, Base, Binding, Bleomycin/*metabolism/pharmacology, Conformation, Crystallization, Crystallography, Data, Drug, Fusion, Genes, Gov't, Microbial/genetics, Models, Molecular, Mutagenesis, Non-U.S., Protein, Proteins/*chemistry/genetics/isolation, Proteins/isolation, purification, purification/metabolism, Recombinant, Relationship, Resistance, Secondary, Sequence, Site-Directed, Sites, Structural, structure, Structure-Activity, Support, X-Ray
@article{,
title = {Crystal structure and site-directed mutagenesis of a bleomycin resistance protein and their significance for drug sequestering},
author = { P. Dumas and M. Bergdoll and C. Cagnon and J. M. Masson},
year = {1994},
date = {1994-01-01},
journal = {EMBO J},
volume = {13},
number = {11},
pages = {2483-92},
abstract = {The antibiotic bleomycin, a strong DNA cutting agent, is naturally produced by actinomycetes which have developed a resistance mechanism against such a lethal compound. The crystal structure, at 2.3 A resolution, of a bleomycin resistance protein of 14 kDa reveals a structure in two halves with the same alpha/beta fold despite no sequence similarity. The crystal packing shows compact dimers with a hydrophobic interface and involved in mutual chain exchange. Two independent solution studies (analytical centrifugation and light scattering) showed that this dimeric form is not a packing artefact but is indeed the functional one. Furthermore, light scattering also showed that one dimer binds two antibiotic molecules as expected. A crevice located at the dimer interface, as well as the results of a site-directed mutagenesis study, led to a model wherein two bleomycin molecules are completely sequestered by one dimer. This provides a novel insight into antibiotic resistance due to drug sequestering, and probably also into drug transport and excretion.},
note = {0261-4189
Journal Article},
keywords = {*Acetyltransferases, &, Acid, Amino, Bacterial, Bacterial/*genetics, Base, Binding, Bleomycin/*metabolism/pharmacology, Conformation, Crystallization, Crystallography, Data, Drug, Fusion, Genes, Gov't, Microbial/genetics, Models, Molecular, Mutagenesis, Non-U.S., Protein, Proteins/*chemistry/genetics/isolation, Proteins/isolation, purification, purification/metabolism, Recombinant, Relationship, Resistance, Secondary, Sequence, Site-Directed, Sites, Structural, structure, Structure-Activity, Support, X-Ray},
pubstate = {published},
tppubtype = {article}
}
The antibiotic bleomycin, a strong DNA cutting agent, is naturally produced by actinomycetes which have developed a resistance mechanism against such a lethal compound. The crystal structure, at 2.3 A resolution, of a bleomycin resistance protein of 14 kDa reveals a structure in two halves with the same alpha/beta fold despite no sequence similarity. The crystal packing shows compact dimers with a hydrophobic interface and involved in mutual chain exchange. Two independent solution studies (analytical centrifugation and light scattering) showed that this dimeric form is not a packing artefact but is indeed the functional one. Furthermore, light scattering also showed that one dimer binds two antibiotic molecules as expected. A crevice located at the dimer interface, as well as the results of a site-directed mutagenesis study, led to a model wherein two bleomycin molecules are completely sequestered by one dimer. This provides a novel insight into antibiotic resistance due to drug sequestering, and probably also into drug transport and excretion.