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Electron redistribution on binding of a substrate to an enzyme: Folate and dihydrofolate reductase
Author(s) -
Bajorath Jürgen,
Kitson David H.,
Fitzgerald George,
Andzelm Jan,
Kraut Joseph,
Hagler Arnold T.
Publication year - 1991
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.340090307
Subject(s) - dihydrofolate reductase , redistribution (election) , enzyme , chemistry , substrate (aquarium) , substrate specificity , biochemistry , biophysics , biology , political science , ecology , politics , law
The migration of electron density of a substrate (folate) on binding to an enzyme (dihydrofolate reductase) is studied by a quantum‐mechanical method originally developed in solid state physics. A significant polarization of the substrate is induced by the enzyme, toward the transition state of the enzymatic reaction, at the same time giving rise to “electronic strain energy” in the substrate and enhanced protein–ligand interactions. The spatial arrangement of protein charges that induces the polarization is identified and found to be structurally conserved for bacterial and vertebrate dihydrofolate reductases.