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Author Harel, M. ♦ Silman, I. ♦ Quinn, D. M. ♦ Nair, H. K. ♦ Sussman, J. L.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword BIOLOGY AND MEDICINE, BASIC STUDIES ♦ CHEMISTRY ♦ ENZYMES ♦ STRUCTURAL CHEMICAL ANALYSIS ♦ X-RAY DIFFRACTION ♦ CHOLINESTERASE ♦ MOLECULAR STRUCTURE ♦ ORGANIC COMPOUNDS ♦ ACETYLCHOLINE ♦ ESTERASES ♦ CRYSTALLOGRAPHY ♦ ENZYME INHIBITORS ♦ ENZYME ACTIVITY
Abstract The structure of a complex of Torpedo californica acetylcholinesterase with the transition state analog inhibitor m-(N, N,N-trimethylammonio)-2,2,2-trifluoroacetophenone has been solved by X-ray crystallographic methods to 2.8 A resolution. Since the inhibitor binds to the enzyme about 10{sup 10}-fold more tightly than the substrate acetylcholine, this complex provides a visual accounting of the enzyme-ligand interactions that provide the molecular basis for the catalytic power of acetylcholinesterase. The acetyl ester hydrolytic specificity of the enzyme is revealed by the interaction of the CF{sub 3} function of the transition state analog with a concave binding site comprised of the residues G119, W233, F288, F290, and F331. The highly geometrically convergent array of enzyme-ligand interactions visualized in the complex described herein envelopes the acylation transition state and sequesters it from solvent, this being consistent with the location of the active site at the bottom of a deep and narrow gorge. 82 refs., 5 figs.
ISSN 00027863
Educational Use Research
Learning Resource Type Article
Publisher Date 1996-03-13
Publisher Place United States
Journal Journal of the American Chemical Society
Volume Number 118
Issue Number 10


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