Document Detail


The substrate-induced conformational change of Mycobacterium tuberculosis mycothiol synthase.
MedLine Citation:
PMID:  16326705     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The structure of the ternary complex of mycothiol synthase from Mycobacterium tuberculosis with bound desacetylmycothiol and CoA was determined to 1.8 A resolution. The structure of the acetyl-CoA-binary complex had shown an active site groove that was several times larger than its substrate. The structure of the ternary complex reveals that mycothiol synthase undergoes a large conformational change in which the two acetyltransferase domains are brought together through shared interactions with the functional groups of desacetylmycothiol, thereby decreasing the size of this large central groove. A comparison of the binary and ternary structures illustrates many of the features that promote catalysis. Desacetylmycothiol is positioned with its primary amine in close proximity and in the proper orientation for direct nucleophilic attack on the si-face of the acetyl group of acetyl-CoA. Glu-234 and Tyr-294 are positioned to act as a general base and general acid to promote acetyl transfer. In addition, this structure provides further evidence that the N-terminal acetyltransferase domain no longer has enzymatic activity and is vestigial in nature.
Authors:
Matthew W Vetting; Michael Yu; Phillip M Rendle; John S Blanchard
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2005-12-02
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  281     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2006 Feb 
Date Detail:
Created Date:  2006-01-30     Completed Date:  2006-05-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2795-802     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461-1602, USA.
Data Bank Information
Bank Name/Acc. No.:
PDB/2C27
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MeSH Terms
Descriptor/Qualifier:
Acetyltransferases / chemistry*
Binding Sites
Coenzyme A / chemistry
Crystallography, X-Ray
Cysteine
Disaccharides / chemistry
Glycopeptides
Inositol
Mycobacterium tuberculosis / enzymology*
Protein Binding
Protein Conformation
Pyrazoles / chemistry
Substrate Specificity
Sulfhydryl Compounds / chemistry
Grant Support
ID/Acronym/Agency:
AI33696/AI/NIAID NIH HHS; AI60899/AI/NIAID NIH HHS; T32 AI07501/AI/NIAID NIH HHS; T32 GM07288/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Disaccharides; 0/Glycopeptides; 0/Pyrazoles; 0/Sulfhydryl Compounds; 0/mycothiol; 52-90-4/Cysteine; 6917-35-7/Inositol; 85-61-0/Coenzyme A; EC 2.3.1.-/Acetyltransferases; EC 2.3.1.-/acetyl-CoA 1-D-myo-inosityl 2-L-cysteinylamido-2-deoxy-alpha-D-glucopyranoside acetyltransferase

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


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