A shifting specificity model for enzyme catalysis.
A new model for general enzyme catalysis challenges the idea that transition state complementarity of enzyme active sites to the reactions they catalyze is the sole source of their catalytic efficacy. The "shifting specificity" model rejects the widely held view that strong interactions of the enzyme with substrate inhibit catalytic efficiency and previously published data are presented which show that a strong interaction of substrate with the enzyme active site actually facilitates its conversion to product. Furthermore, this new model defines a role for the entire enzyme molecule unlike most theories of enzyme catalysis which are concerned only with the interaction of the active site with substrate. This shifting specificity model for general enzyme catalysis may be expressed succinctly as: (i) enzymes have evolved to bind substrates; (ii) enzyme/substrate complexes have evolved to bind transition states; (iii) a stronger interaction of substrate with the enzyme facilitates a more rapid conversion to product. This last effect results from a more efficient modulation of the global enzyme conformation by tight-binding substrates. It is suggested that the addition of atomic mass to the enzyme, which interacts with the enzyme in the same manner in which the enzyme domains interact with one another, must alter the low-frequency, global vibrations of the enzyme to produce a different overall conformation. Nature has selected for that conformational change which shifts the active site complementarity from substrate-specific to transition state-specific. Thus, this model suggests a means for an efficient realization of the substrate-binding energy in the transition state of the reaction. General aspects of this model are discussed in light of the current view of enzyme catalysis.
Britt
B M
BM
INC-14 MS C34S, Los Alamos National Laboratory, NM 87545.
D002384:Catalysis; D004798:Enzymes / Q000378:metabolism*; D008956:Models, Chemical; D013379:Substrate Specificity
D004798:Enzymes