title: Aminoglycoside 2'-N-acetyltransferase from Mycobacterium tuberculosis in complex with coenzyme A and aminoglycoside substrates.
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.
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Vetting
authors.forename: Subray S
authors.initials: SS
authors.lastname: Hegde
authors.forename: Farah
authors.initials: F
authors.lastname: Javid-Majd
authors.forename: John S
authors.initials: JS
authors.lastname: Blanchard
authors.forename: Steven L
authors.initials: SL
authors.lastname: Roderick
mesh_terms: D000123:Acetyltransferases / Q000737:chemistry / Q000378:metabolism*; D000617:Aminoglycosides / Q000737:chemistry / Q000378:metabolism*; D002240:Carbohydrate Sequence; D003065:Coenzyme A / Q000378:metabolism*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D011487:Protein Conformation; D013379:Substrate Specificity
chemical_list: D000617:Aminoglycosides; D000123:Acetyltransferases; C443113:aminoglycoside 2'-N-acetyltransferase; D003065:Coenzyme A