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Cooperative binding of transition states in enzymatic catalysis
Author(s) -
Jacchieri S. G.
Publication year - 2009
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560360724
Subject(s) - cooperativity , allosteric regulation , cooperative binding , chemistry , transition state , substrate (aquarium) , enzyme catalysis , cofactor , catalysis , allosteric enzyme , binding site , enzyme , transition (genetics) , nicotinamide adenine dinucleotide , transition state analog , stereochemistry , active site , nad+ kinase , biochemistry , biology , ecology , gene
A thermodynamic reasoning is used to show that transition states as well as substrates may be bound cooperatively by enzymes and equations that relate the free energies of substrate binding to free energies of transition‐state binding are derived. The consequences of cooperative transition‐state binding are, however, quite distinct from the consequences of cooperative substrate binding. Whereas the latter accounts for the sensitivity of the reaction rate to substrate concentration, the former may be the cause of a specificity to products and mechanisms of catalysis. It is shown that when there is a strong anticooperative interaction, as in half of the sites reactivity, the half‐occupied enzyme molecule has a greater affinity for the transition state than for the substrate. In that case, interaction between active sites can be part of catalysis. The roles of cooperative and anticooperative substrate and transition‐state binding in reactions that yield chiral products from nonchiral substrates are discussed. Nicotinamide adenine dinucleotide‐dependent dehydrogenases provide many instances of such reactions. Cooperative binding of the transition state, the coenzyme, and the substrate are related in this case, because coenzyme and substrate form the transition state. It is argued that apart from the well‐known role played by allosteric interactions in enzyme regulation, cooperativity and anticooperativity are, in many cases, related to enzyme specificity.