Aminoglycoside 2′-N-acetyltransferase from Mycobacterium tuberculosis in complex with coenzyme A and aminoglycoside substrates

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

Research output: Contribution to journalArticle

107 Citations (Scopus)

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

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aminoglycoside 2'-N-acetyltransferase
Aminoglycosides
Coenzyme A
Mycobacterium tuberculosis
Substrates
Ribostamycin
Acetylation
Acetyltransferases
Tobramycin
Kanamycin
Reducing Agents
Enzymes
Mycobacterium
Structural analysis
Hydroxyl Radical
Oxidation-Reduction
Crystal structure
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Structural Biology

Cite this

Aminoglycoside 2′-N-acetyltransferase from Mycobacterium tuberculosis in complex with coenzyme A and aminoglycoside substrates. / Vetting, Matthew W.; Hegde, Subray; Javid-Majd, Farah; Blanchard, John S.; Roderick, Steven L.

In: Nature Structural Biology, Vol. 9, No. 9, 09.2002, p. 653-658.

Research output: Contribution to journalArticle

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