A perspective on enzyme catalysis.
The seminal hypotheses proposed over the years for enzymatic catalysis are scrutinized. The historical record is explored from both biochemical and theoretical perspectives. Particular attention is given to the impact of molecular motions within the protein on the enzyme's catalytic properties. A case study for the enzyme dihydrofolate reductase provides evidence for coupled networks of predominantly conserved residues that influence the protein structure and motion. Such coupled networks have important implications for the origin and evolution of enzymes, as well as for protein engineering.
Benkovic
Stephen J
SJ
Department of Chemistry, 152 Davey Laboratory, Pennsylvania State University, University Park, PA 16802, USA. sjb1@psu.edu
Hammes-Schiffer
Sharon
S
D001665:Binding Sites; D002384:Catalysis; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008956:Models, Chemical; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism*; D013816:Thermodynamics
D004798:Enzymes; D013762:Tetrahydrofolate Dehydrogenase