Transient kinetics of aminoglycoside phosphotransferase(3′)-IIIa reveals a potential drug target in the antibiotic resistance mechanism

More about Open Access at the Crick


Aminoglycoside phosphotransferases are bacterial enzymes responsible for the inactivation of aminoglycoside antibiotics by O-phosphorylation. It is important to understand the mechanism of enzymes in order to find efficient drugs. Using rapid-mixing methods, we studied the transient kinetics of aminoglycoside phosphotransferase(3')-IIIa. We show that an ADP-enzyme complex is the main steady state intermediate. This intermediate interacts strongly with kanamycin A to form an abortive complex that traps the enzyme in an inactive state. A good strategy to prevent the inactivation of aminoglycosides would be to develop uncompetitive inhibitors that interact with this key ADP-enzyme complex.

Journal details

Journal FEBS Letters
Volume 586
Issue number 23
Pages 4223-4227
Publication date


Crick labs/facilities

Crick authors

Crick First author
Crick Corresponding author