Conference paper

Methanesulfonyl Fluoride: A Probe of Substrate Interactions in the Catalytic Site of Acetylcholinesterase

R. M. Krupka ; Research Institute, Research Branch, Agriculture Canada, University Sub Post Office, London, Ontario, N6A 5B7, Canada

Abstract

Methanesulfonyl fluoride, which reacts at the catalytic S!ite
of acetylcholinesterase causing inactivation, is a useful probe of
substrate binding. This is because molecules absorbed in or near
the active center appear to protect the enzyme only if, by interacting
strongly with the esteratic s.ite, they physically obstruct its
approach. Its reaction is not disturbed by non-specific adsorption
of these molecules in regions adjoining the active center, and ~s
comparatively insensitive to conditions that reversibly denature the
enzyme. The binding of three classes of substrates is discussed:
acetylcholine analogs, phenyl esters, and indophenyl acetate. Acetylcholine fits into an active center crevice and covers both the anionic and esteratic sites, but bulkier analogs, which cannot fully penetrate, are held primarily at the anionic site and adjoining non-polar
regions, with weak and intermittent attraction to the esteratic site.
Phenyl esters are bound within the crevice, over the esteratic site.
Indophenyl acetate is adsorbed on the margin of the active center,
covering neither the anionic nor esteratic site.

Keywords

Hrčak ID:

196593

URI

https://hrcak.srce.hr/196593

Publication date:

3.12.1975.

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