Document Detail

Ligand-induced fit in mycobacterial MabA: the sequence-specific C-terminus locks the conformational change.
MedLine Citation:
PMID:  15977159     Owner:  NLM     Status:  MEDLINE    
The protein MabA of Mycobacterium tuberculosis is a beta-ketoacyl reductase (KAR) and catalyses one of the four steps of the fatty acid elongation system FAS-II. The crystal structures of different KARs revealed a significant rearrangements of the active site between a "closed" inactive conformation and an "open" and active form in presence of the cofactor. MabA is a potential therapeutic target. However, only the structure of the "closed" form was obtained and rational drug design requires the structure of the active form. Here we described the sequences and structures analysis of the KARs to stabilize the "open form" in MabA. The crystal structure of a mutated MabA protein was then solved in both inactive and active form. The crystal structure of the wild-type MabA in the presence of NADP was also solved and showing a mixture of the two mutually exclusive conformations. This new structure of MabA is analyzed in view of its distinctive enzymatic and structural properties and those of related enzymes.
Martin Cohen-Gonsaud; Stéphanie Ducasse-Cabanot; Annaïk Quemard; Gilles Labesse
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proteins     Volume:  60     ISSN:  1097-0134     ISO Abbreviation:  Proteins     Publication Date:  2005 Aug 
Date Detail:
Created Date:  2005-07-18     Completed Date:  2006-05-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8700181     Medline TA:  Proteins     Country:  United States    
Other Details:
Languages:  eng     Pagination:  392-400     Citation Subset:  IM    
Copyright Information:
(c) 2005 Wiley-Liss, Inc.
Centre de Biochimie Structurale INSERM U554, CNRS UMR5048, UM1, Montpellier cedex, France.
Data Bank Information
Bank Name/Acc. No.:
PDB/1EDO;  1I01;  1ZID
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MeSH Terms
Alcohol Oxidoreductases / chemistry*
Amino Acid Sequence
Binding Sites
Cesium / chemistry
Cloning, Molecular
Crystallography, X-Ray
Databases, Protein
Escherichia coli / metabolism
Models, Molecular
Models, Statistical
Molecular Conformation
Molecular Sequence Data
Mutagenesis, Site-Directed
Mycobacterium tuberculosis / metabolism*
Protein Conformation
Protein Structure, Tertiary
Sequence Homology, Amino Acid
Substrate Specificity
Reg. No./Substance:
0/Ligands; 7440-46-2/Cesium; EC 1.1.-/Alcohol Oxidoreductases; EC reductase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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