The substrate-induced conformational change of mycobacterium tuberculosis mycothiol synthase

Matthew W. Vetting, Michael Yu, Phillip M. Rendle, John S. Blanchard

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The structure of the ternary complex of mycothiol synthase from Mycobacterium tuberculosis with bound desacetylmycothiol and CoA was determined to 1.8 Å 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.

Original languageEnglish (US)
Pages (from-to)2795-2802
Number of pages8
JournalJournal of Biological Chemistry
Volume281
Issue number5
DOIs
StatePublished - Feb 3 2006

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Acetyl Coenzyme A
Mycobacterium tuberculosis
N-Terminal Acetyltransferases
Acetyltransferases
Substrates
Coenzyme A
Catalysis
Functional groups
Amines
Catalytic Domain
Acids
acetyl-CoA 1-D-myo-inosityl 2-L-cysteinylamido-2-deoxy-alpha-D-glucopyranoside acetyltransferase

ASJC Scopus subject areas

  • Biochemistry

Cite this

The substrate-induced conformational change of mycobacterium tuberculosis mycothiol synthase. / Vetting, Matthew W.; Yu, Michael; Rendle, Phillip M.; Blanchard, John S.

In: Journal of Biological Chemistry, Vol. 281, No. 5, 03.02.2006, p. 2795-2802.

Research output: Contribution to journalArticle

Vetting, Matthew W. ; Yu, Michael ; Rendle, Phillip M. ; Blanchard, John S. / The substrate-induced conformational change of mycobacterium tuberculosis mycothiol synthase. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 5. pp. 2795-2802.
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