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The path to the transition state in enzyme reactions: a survey of catalytic efficiencies
Author(s) -
Snider Mark G.,
Temple Brenda S.,
Wolfenden Richard
Publication year - 2004
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.761
Subject(s) - chemistry , substrate (aquarium) , enzyme , affinities , transition state , transition state analog , catalysis , chemical physics , stereochemistry , active site , biochemistry , ecology , biology
A survey of k cat / K m values supports the view that most enzymes combine with substrates at rates that approach the limits imposed by diffusional encounter. The closeness of that approach precludes the obligate participation of any rare species of the substrate, or any rare species of the enzyme, in productive binding. Proceeding from the ground state through the transition state, the enzyme–substrate complex is assumed to remain in a state of quasi‐equilibrium with the free enzyme and the unbound substrate in solution. Because the forces of attraction between an enzyme and substrate approach a maximum in the transition state for substrate transformation, the enzyme and substrate are also likely to approach a maximal state of distortion from their native ground‐state structures at that stage in the reaction, furnishing a natural explanation of induced fit. There is now abundant evidence, from mutations of enzymes and substrates, that interactions between the enzyme and substrate, using ordinary chemical forces of attraction, are so strongly synergistic that they may suffice to explain the very high affinities that are achieved in the transition state. Copyright © 2004 John Wiley & Sons, Ltd.