Kanamycin kinase

Aminoglycoside-3'-phosphotransferase (APH(3')), also known as aminoglycoside kinase, is an enzyme that primarily catalyzes the addition of phosphate from ATP to the 3'-hydroxyl group of a 4,6-disubstituted aminoglycoside, such as kanamycin. However, APH(3') has also been found to phosphorylate at the 5'-hydroxyl group in 4,5-disubstituted aminoglycosides, which lack a 3'-hydroxyl group, and to diphosphorylate hydroxyl groups in aminoglycosides that have both 3'- and 5'-hydroxyl groups. Primarily positively charged at biological conditions, aminoglycosides bind to the negatively charged backbone of nucleic acids to disrupt protein synthesis, effectively inhibiting bacterial cell growth. APH(3') mediated phosphorylation of aminoglycosides effectively disrupts their mechanism of action, introducing a phosphate group that reduces their binding affinity due to steric hindrances and unfavorable electrostatic interactions. APH(3') is primarily found in certain species of gram-positive bacteria.