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The Structure of an Actively Exchanging Complex between Carboxypeptidase A and a Substrate Analogue

Rees, Douglas C. and Honzatko, Richard B. and Lipscomb, William N. (1980) The Structure of an Actively Exchanging Complex between Carboxypeptidase A and a Substrate Analogue. Proceedings of the National Academy of Sciences of the United States of America, 77 (6). pp. 3288-3291. ISSN 0027-8424. PMCID PMC349600. https://resolver.caltech.edu/CaltechAUTHORS:20150210-100541503

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Abstract

An x-ray diffraction study at 2.8 Å resolution has yielded the structure of a complex between bovine carboxypeptidase A (peptidyl-L-amino-acid hydrolase, EC 3.4.17.1) and (-)-2-benzyl-3-p-methoxybenzoylpropionic acid. This substrate is an analogue of N-(p-methoxy)-benzoylphenylalanine, in which the amide NH is replaced by CH_2. T. Sugimoto and E T. Kaiser (1979) J. Am. Chem. Soc. 101, 39469--3951] have shown that this complex catalyzes stereospecific exchange of that proton of the CH_2 group which is in the R configuration. Our structure of this complex suports the model proposed by Sugimoto and Kaiser and is very similar to the productive peptide binding mode suggested by Lipscomb et al. [Lipscomb, W. N., Hartsuck, J. A., Reeke, G. N., Quiocho, F. A., Bethge, P. A., Ludwig, M. L., Steitz, T. A., Muirhead, H. & Coppola. J. C. (1968) Brookhaven Symp. Biol. 21, 24--90]. The proposed roles of glutamic acid 270 in the proton exchange and the interaction of zinc with the carbonyl group of the substrate are consistent with the observed structure.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://www.pnas.org/content/77/6/3288PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC349600/PubMed CentralArticle
ORCID:
AuthorORCID
Rees, Douglas C.0000-0003-4073-1185
Additional Information:© 1980 National Academy of Sciences. Contributed by William N. Lipscomb, March 18, 1980. We thank E.T. Kaiser for the sample of this ketonic substrate and the National Institutes of Health, Grant GM 06920, for support of this research. W.N.L. thanks the Alexander von Humboldt Foundation for an award which facilitated this study. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.
Funders:
Funding AgencyGrant Number
NIHGM 06920
Alexander von Humboldt FoundationUNSPECIFIED
Subject Keywords:enzyme catalysis; proteases; protein crystallography
Issue or Number:6
PubMed Central ID:PMC349600
Record Number:CaltechAUTHORS:20150210-100541503
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150210-100541503
Official Citation:D C Rees, R B Honzatko, and W N Lipscomb Structure of an actively exchanging complex between carboxypeptidase A and a substrate analogue PNAS 1980 77 (6) 3288-3291
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:54657
Collection:CaltechAUTHORS
Deposited By: SWORD User
Deposited On:11 Feb 2015 00:01
Last Modified:03 Oct 2019 07:59

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