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Science 23 November 1990:
Vol. 250. no. 4984, pp. 1135 - 1139
DOI: 10.1126/science.2251500
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Articles

Science, Vol 250, Issue 4984, 1135-1139
Copyright © 1990 by American Association for the Advancement of Science

articles

The enzymic nature of antibody catalysis: development of multistep kinetic processing

SJ Benkovic, JA Adams, CL Borders Jr, KD Janda, and RA Lerner

Pennsylvania State University, Department of Chemistry, University Park 16802.

Detailed kinetic investigations of a catalytic antibody that promotes the hydrolyses of an anilide and phenyl ester show that this catalyst uses a multistep kinetic sequence resembling that found in serine proteases to hydrolyze its substrates, although antibody was elicited to a single transition-state analog. Like the serine proteases the antibody catalyzes the hydrolysis reactions through a putative covalent intermediate, but unlike the enzymes it may use hydroxide ion to cleave the intermediates. Nevertheless, the antibody is a potent catalyst with turnover at higher pH values rivaling that of chymotrypsin. This analysis also reveals that turnover by the antibody is ultimately limited by product desorption, suggesting that improvements in catalytic efficiency may be achieved by judicious changes in the structure of the substrate, so that it is not superimposable on that of the eliciting hapten.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
X-ray structures of a hydrolytic antibody and of complexes elucidate catalytic pathway from substrate binding and transition state stabilization through water attack and product release.
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Immuno-PCR: very sensitive antigen detection by means of specific antibody-DNA conjugates.
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At the crossroads of chemistry and immunology: catalytic antibodies.
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An unexpectedly efficient catalytic antibody operating by ping-pong and induced fit mechanisms.
P Wirsching, J. Ashley, S. Benkovic, K. Janda, and R. Lerner (1991)
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