title: Electron redistribution on binding of a substrate to an enzyme: folate and dihydrofolate reductase.
abstract: 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.
authors.affiliation: Biosym Technologies, Inc., San Diego, California 92121.
authors.forename: J
authors.initials: J
authors.lastname: Bajorath
authors.forename: D H
authors.initials: DH
authors.lastname: Kitson
authors.forename: G
authors.initials: G
authors.lastname: Fitzgerald
authors.forename: J
authors.initials: J
authors.lastname: Andzelm
authors.forename: J
authors.initials: J
authors.lastname: Kraut
authors.forename: A T
authors.initials: AT
authors.lastname: Hagler
mesh_terms: D001665:Binding Sites; D002384:Catalysis; D004583:Electrons; D005492:Folic Acid / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D011789:Quantum Theory; D013379:Substrate Specificity; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry / Q000378:metabolism*; D014961:X-Ray Diffraction
chemical_list: D005492:Folic Acid; D013762:Tetrahydrofolate Dehydrogenase