Inhibition of Aminoglycoside Antibiotic Resistance Enzymes by Protein Kinase Inhibitors*

Bacterial resistance to the aminoglycoside antibiotics is manifested primarily through the expression of enzymes which covalently modify these drugs. One important mechanism of aminoglycoside modification is through ATP-dependent O-phosphorylation, catalyzed by a family of aminoglycoside kinases. The structure of one of these kinases, APH(3')-IIIa has recently been determined by x-ray crystallography, and the general fold is strikingly similar …