title: Temporally overlapped but uncoupled motions in dihydrofolate reductase catalysis.
abstract: Temporal correlations between protein motions and enzymatic reactions are often interpreted as evidence for catalytically important motions. Using dihydrofolate reductase as a model system, we show that there are many protein motions that temporally overlapped with the chemical reaction, and yet they do not exhibit the same kinetic behaviors (KIE and pH dependence) as the catalyzed chemical reaction. Thus, despite the temporal correlation, these motions are not directly coupled to the chemical transformation, and they might represent a different part of the catalytic cycle or simply be the product of the intrinsic flexibility of the protein.
authors.affiliation: Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: C Tony
authors.initials: CT
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Nina M
authors.initials: NM
authors.lastname: Goodey
authors.forename: Philip
authors.initials: P
authors.lastname: Hanoian
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Benkovic
mesh_terms: D055162:Biocatalysis; D006860:Hydrogen Bonding; D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry*
chemical_list: D013762:Tetrahydrofolate Dehydrogenase