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 language | English (US) |
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Pages (from-to) | 653-658 |
Number of pages | 6 |
Journal | Nature Structural Biology |
Volume | 9 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2002 |
ASJC Scopus subject areas
- Structural Biology
- Biochemistry
- Genetics