Cooper B F, Rudolph F B
Department of Biochemistry and Cell Biology, Rice University, Houston, Texas 77251, USA.
Methods Enzymol. 1995;249:188-211. doi: 10.1016/0076-6879(95)49036-1.
A product inhibition study provides important insight into the binding mechanism of an enzyme, especially in the identification of abortive complexes, but seldom is it the only tool required to solve the mechanism completely. Always keep in mind that more than one mechanism may be consistent with the patterns, and several alternative schemes should be analyzed by including abortive complexes and, as a last resort, isomerization steps or slow product release steps in the interpretation. Support for the proposed mechanism should be garnered from other data, such as kinetic studies with alternative substrates and competitive inhibitors, positional and molecular isotope exchange studies, binding studies, and isotope effects. A well-characterized binding mechanism complete with the identification of abortive complexes is even more important as rational drug design becomes more prevalent. Product inhibition studies represent an important tool that is relatively easy to apply to gain significant information about the binding mechanism of most enzymes.
