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Science 3 May 1991:
Vol. 252. no. 5006, pp. 680 - 685
DOI: 10.1126/science.2024120
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Articles

Science, Vol 252, Issue 5006, 680-685
Copyright © 1991 by American Association for the Advancement of Science

articles

An unexpectedly efficient catalytic antibody operating by ping-pong and induced fit mechanisms

P Wirsching, JA Ashley, SJ Benkovic, KD Janda, and RA Lerner

Department of Chemistry, Scripps Research Institute, La Jolla, CA 92037.

A transition state analogue was used to produce a mouse antibody that catalyzes transesterification in water. The antibody behaves as a highly efficient catalyst with a covalent intermediate and the characteristic of induced fit. While some features of the catalytic pathway were programmed when the hapten was designed and reflect favorable substrate-antibody interactions, other features are a manifestation of the chemical potential of antibody diversity. The fact that antibodies recapitulate mechanisms and pathways previously thought to be a characteristic of highly evolved enzymes suggests that once an appropriate binding cavity is achieved, reaction pathways commensurate with the intrinsic chemical potential of proteins ensue.


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