title: Network of coupled promoting motions in enzyme catalysis.
abstract: A network of coupled promoting motions in the enzyme dihydrofolate reductase is identified and characterized. The present identification is based on genomic analysis for sequence conservation, kinetic measurements of multiple mutations, and mixed quantum/classical molecular dynamics simulations of hydride transfer. The motions in this network span time scales of femtoseconds to milliseconds and are found on the exterior of the enzyme as well as in the active site. This type of network has broad implications for an expanded role of the protein fold in catalysis as well as ancillaries such as the engineering of altered protein function and the action of drugs distal to the active site.
authors.affiliation: Department of Chemistry, 152 Davey Laboratory, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Pratul K
authors.initials: PK
authors.lastname: Agarwal
authors.forename: Salomon R
authors.initials: SR
authors.lastname: Billeter
authors.forename: P T Ravi
authors.initials: PT
authors.lastname: Rajagopalan
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Benkovic
authors.forename: Sharon
authors.initials: S
authors.lastname: Hammes-Schiffer
mesh_terms: D000818:Animals; D002384:Catalysis; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D013762:Tetrahydrofolate Dehydrogenase