title: Electric Fields and Enzyme Catalysis.
abstract: What happens inside an enzyme's active site to allow slow and difficult chemical reactions to occur so rapidly? This question has occupied biochemists' attention for a long time. Computer models of increasing sophistication have predicted an important role for electrostatic interactions in enzymatic reactions, yet this hypothesis has proved vexingly difficult to test experimentally. Recent experiments utilizing the vibrational Stark effect make it possible to measure the electric field a substrate molecule experiences when bound inside its enzyme's active site. These experiments have provided compelling evidence supporting a major electrostatic contribution to enzymatic catalysis. Here, we review these results and develop a simple model for electrostatic catalysis that enables us to incorporate disparate concepts introduced by many investigators to describe how enzymes work into a more unified framework stressing the importance of electric fields at the active site.
authors.affiliation: Proteins and Nucleic Acid Chemistry Division, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, United Kingdom; email: sf537@cam.ac.uk.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Fried
authors.affiliation: Department of Chemistry, Stanford University, Stanford, California 94305; email: sboxer@stanford.edu.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Boxer
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D055162:Biocatalysis; D020134:Catalytic Domain; D015870:Gene Expression; D006867:Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007664:Ketosteroids / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D009154:Mutation; D011549:Pseudomonas / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D013055:Spectrophotometry, Infrared / Q000379:methods; D055672:Static Electricity; D013251:Steroid Isomerases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D007664:Ketosteroids; D006867:Hydrolases; C084333:4-chlorobenzoyl coenzyme A dehalogenase; D013251:Steroid Isomerases
keywords: electric fields; enzyme electrostatics; infrared spectroscopy; preorganization; protein biophysics; vibrational Stark effect