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

Article Details

Citation

Copy to clipboard

Vetting MW, Hegde SS, Javid-Majd F, Blanchard JS, Roderick SL

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

Nat Struct Biol. 2002 Sep;9(9):653-8.

PubMed ID

12161746 [ View in PubMed

]

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.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Coenzyme A	Aminoglycoside 2'-N-acetyltransferase	Protein	Mycobacterium tuberculosis	Unknown	Ligand	Details
Kanamycin	Aminoglycoside 2'-N-acetyltransferase	Protein	Mycobacterium tuberculosis	Unknown	Substrate	Details

Polypeptides

Name	UniProt ID
Aminoglycoside 2'-N-acetyltransferase	P9WQG9	Details