How do enzymes work?

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Science  28 Oct 1988:
Vol. 242, Issue 4878, pp. 533-540
DOI: 10.1126/science.3051385


The principle of transition-state stabilization asserts that the occurrence of enzymic catalysis is equivalent to saying that an enzyme binds the transition state much more strongly than it binds the ground-state reactants. An outline of the origin and gradual acceptance of this idea is presented, and elementary transition-state theory is reviewed. It is pointed out that a misconception about the theory has led to oversimplification of the accepted expression relating catalysis and binding, and an amended expression is given. Some implications of the transition-state binding principle are then explored. The amended expression suggests that internal molecular dynamics may also play a role in enzymic catalysis. Although such effects probably do not make a major contribution, their magnitude is completely unknown. Two examples of recent advances due to application of the transition-state binding principle are reviewed, one pertaining to the zinc protease mechanism and the other to the generation of catalytic antibodies.