Aminoglycoside 2'-N-acetyltransferase from Mycobacterium tuberculosis in complex with coenzyme A and aminoglycoside substrates.
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.
Vetting
Matthew W
MW
Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
Hegde
Subray S
SS
Javid-Majd
Farah
F
Blanchard
John S
JS
Roderick
Steven L
SL
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
D000617:Aminoglycosides; D000123:Acetyltransferases; C443113:aminoglycoside 2'-N-acetyltransferase; D003065:Coenzyme A