Relating protein motion to catalysis.
This review examines the linkage between protein conformational motions and enzyme catalysis. The fundamental issues related to this linkage are probed in the context of two enzymes that catalyze hydride transfer, namely dihydrofolate reductase and liver alcohol dehydrogenase. The extensive experimental and theoretical studies addressing the role of protein conformational changes in these enzyme reactions are summarized. Evidence is presented for a network of coupled motions throughout the protein fold that facilitate the chemical reaction. This network is comprised of fast thermal motions that are in equilibrium as the reaction progresses along the reaction coordinate and that lead to slower equilibrium conformational changes conducive to the chemical reaction.
Hammes-Schiffer
Sharon
S
Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania 16802, USA. shs@chem.psu.edu
Benkovic
Stephen J
SJ
D000426:Alcohol Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D002384:Catalysis; D006801:Humans; D008099:Liver / Q000201:enzymology; D008958:Models, Molecular; D008962:Models, Theoretical; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation; D017510:Protein Folding; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D000426:Alcohol Dehydrogenase; D013762:Tetrahydrofolate Dehydrogenase