Aminoglycoside 2′-n-acetyltransferase from mycobacterium tuberculosis in complex with coenzyme a and aminoglycoside substrates

Matthew W. Vetting, Subray S. Hegde, Farah Javid-Majd, John S. Blanchard, Steven L. Roderick

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

AAC(2′)-Ic catalyzes the coenzyme A (CoA)-dependent acetylation of the 2′ hydroxyl or amino group of a broad spectrum of aminoglycosides. The crystal structure of the AAC(2′)-Ic from Mycobacterium tuberculosis has been determined in the apo enzyme form and in ternary complexes with CoA and either tobramycin, kanamycin A or ribostamycin, representing the first structures of an aminoglycoside acetyltransferase bound to a drug. The overall fold of AAC(2′)-Ic places it in the GCN5-related N-acetyltransferase (GNAT) superfamily. Although the physiological function of AAC(2′)-Ic is uncertain, a structural analysis of these high-affinity aminoglycoside complexes suggests that the enzyme may acetylate a key biosynthetic intermediate of mycothiol, the major reducing agent in mycobacteria, and participate in the regulation of cellular redox potential.

Original languageEnglish (US)
Pages (from-to)653-658
Number of pages6
JournalNature structural biology
Volume9
Issue number9
DOIs
StatePublished - Sep 2002

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Genetics

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