Bisubstrate inhibition: Theory and application to N-acetyltransferases.
Bisubstrate inhibitors represent a potentially powerful group of compounds that have found significant therapeutic utility. Although these compounds have been synthesized and tested against a number of enzymes that catalyze sequential bireactant reactions, the detailed theory for predicting the expected patterns of inhibition against the two substrates for various bireactant kinetic mechanisms has, heretofore, not been presented. We have derived the rate equations for all likely sequential bireactant mechanisms and provide two examples in which bisubstrate inhibitors allow the kinetic mechanism to be determined. Bisubstrate inhibitor kinetics is a powerful diagnostic for the determination of kinetic mechanisms.
Yu
Michael
M
Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
Magalhães
Maria L B
ML
Cook
Paul F
PF
Blanchard
John S
JS
D000105:Acetyl Coenzyme A / Q000138:chemical synthesis; D000123:Acetyltransferases / Q000037:antagonists & inhibitors*; D003065:Coenzyme A / Q000138:chemical synthesis; D007700:Kinetics; D008962:Models, Theoretical; D013379:Substrate Specificity
D000105:Acetyl Coenzyme A; D000123:Acetyltransferases; D003065:Coenzyme A