Aminoglycoside nucleotidyltransferases

Unit, [tg/mL Kan, kanamycin S. aureus, Staphylococcus aureus P. aeruginosa, Pseudomonas aeruginosa AAC, aminoglycoside acetyltransferase ANT, aminoglycoside nucleotidyltransferase Perm, mutant, mutant strain impermeable to kanamycin A and B. 

Fig. 13.5 Structure of kanamycin B showing system of ring numbering and sites of action of some aminoglycosidemodifying enzymes. AAC, aminoglycoside acetyltransferase ANT, aminoglycoside nucleotidyltransferase and APH, aminoglycoside phosphotransferase.

Beside AAC enzymes two different enzyme classes, nucleotidyltransferases (ANT enzymes), and phosphotransferases (APH enzymes) modify the hydroxyl groups of aminocyclitol-aminoglycoside antibiotics. 

Resistance can be caused by 1) decreased uptake of drug when the oxygen-dependent transport system for aminoglycosides is absent an altered receptor where the 30S ribosomal subunit binding site has a lowered affinity for aminoglycosides plasmid-associated synthesis of enzymes (for example, acetyltransferases, nucleotidyltransferases, and phosphotransferases) that modify and inactivate aminoglycoside... 

D. R. Ekman, E. L. DiGiammarino, E. Wright, E. D. Witter, and E. H. Serpersu, Cloning, overexpression, and purification of aminoglycoside antibiotic nucleotidyltransferase (2" )-Ia conformational studies with bound substrates. Biochemistry, 40 (2001) 7017-7024. 

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