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Catalysis by Chimeric Proteins: Conversion of a β-lactamase to a D,D-Carboxypeptidase

Labgold, Marc R. and Chang, Yie-Hwa and Richards, John H. (1990) Catalysis by Chimeric Proteins: Conversion of a β-lactamase to a D,D-Carboxypeptidase. In: Current Research in Protein Chemistry. No.1. Academic Press Inc. , San Diego, CA, pp. 489-497. ISBN 978-0-12-721955-4. https://resolver.caltech.edu/CaltechAUTHORS:20150430-080918756

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Abstract

The β-lactam antibiotics are the substrates of two large groups of bacterial enzymes. The first group, the penicillin binding proteins (PBPs), function as the D,D-carboxypeptidases (Cpase) and transpeptidases (Tpase) involved in the crosslinking of peptidoglycan in the final stage of cell wall biosynthesis (1). By catalyzing the hydrolysis of a C-terminal D-Ala-D-Ala dipeptide followed by transfer of the free amino terminus to another peptide chain, these enzymes stabilize the bacterial cell wall against hypotonic lysis (Figure 1). The PBPs are also able to bind the β-lactam antibiotics as structural analogues to the D-Ala-D-Ala dipeptide, however opening of the lactam bond by these enzymes leads to a stable acyl-enzyme complex. This slow reversible binding of the antibiotics prevents the crosslinking that is catalyzed by the PBPs and that is necessary for cell viability.


Item Type:Book Section
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1016/B978-0-12-721955-4.50051-8DOIArticle
http://www.sciencedirect.com/science/article/pii/B9780127219554500518PublisherArticle
Additional Information:© 1990 by Academic Press, Inc. Available online 6 November 2012. This research was supported by NIH Grant GM 16424 and by the Caltech Consortium in Chemistry and Chemical Engineering; Founding Members: E.I. duPont de Nemours and Company Inc., Eastman Kodak Company, Minnesota Mining and Manufacturing Company, and Shell Oil Company Foundation.
Funders:
Funding AgencyGrant Number
NIHGM 16424
E. I. duPont de Nemours and Company Inc.UNSPECIFIED
Eastman Kodak CompanyUNSPECIFIED
Minnesota Mining and Manufacturing CompanyUNSPECIFIED
Shell Oil Company FoundationUNSPECIFIED
Issue or Number:1
Record Number:CaltechAUTHORS:20150430-080918756
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150430-080918756
Official Citation:Marc R. Labgold, Yie-Hwa Chang and John H. Richards, 45 - Catalysis by Chimeric Proteins: Conversion of a β-Iactamase to a D,D-Carboxypeptidase1, In Current Research in Protein Chemistry, edited by Joseph J. Villafranca, Academic Press, 1990, Pages 489-497, ISBN 9780127219554, http://dx.doi.org/10.1016/B978-0-12-721955-4.50051-8. (http://www.sciencedirect.com/science/article/pii/B9780127219554500518)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:57102
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:30 Apr 2015 20:32
Last Modified:03 Oct 2019 08:21

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