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The role of enzyme distortion in the single displacement mechanism of family 19 chitinases

Brameld, Ken A. and Goddard, William A., III (1998) The role of enzyme distortion in the single displacement mechanism of family 19 chitinases. Proceedings of the National Academy of Sciences of the United States of America, 95 (8). pp. 4276-4281. ISSN 0027-8424. PMCID PMC22479. doi:10.1073/pnas.95.8.4276.

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By using molecular dynamics simulations, we have examined the binding of a hexaNAG substrate and two potential hydrolysis intermediates (an oxazoline ion and an oxocarbenium ion) to a family 19 barley chitinase. We find the hexaNAG substrate binds with all sugars in a chair conformation, unlike the family 18 chitinase which causes substrate distortion. Glu 67 is in a position to protonate the anomeric oxygen linking sugar residues D and E whereas Asn 199 serves to hydrogen bond with the C2′ N-acetyl group of sugar D, thus preventing the formation of an oxazoline ion intermediate. In addition, Glu 89 is part of a flexible loop region allowing a conformational change to occur within the active site to bring the oxocarbenium ion intermediate and Glu 89 closer by 4–5 Å. A hydrolysis product with inversion of the anomeric configuration occurs because of nucleophilic attack by a water molecule that is coordinated by Glu 89 and Ser 120. Issues important for the design of inhibitors specific to family 19 chitinases over family 18 chitinases also are discussed.

Item Type:Article
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URLURL TypeDescription CentralArticle
Goddard, William A., III0000-0003-0097-5716
Additional Information:© 1998 The National Academy of Sciences. Contributed by William A. Goddard III, January 26, 1998. This research was funded by the Department of Energy-Biological and Chemical Technologies Research Program (DE-FG36–93CH105 81). The facilities of the Materials and Process Simulation Center also are supported by grants from National Science Foundation (CHE 95-22179 and ASC 92-100368), Chevron Petroleum Technology Co., Saudi Aramco, Asahi Chemical, Owens-Corning, Exxon, Chevron Chemical Company, Chevron Research and Technology Co., Avery-Dennison, Hercules, BP Chemical, and Beckman Institute. 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.
Funding AgencyGrant Number
Department of Energy (DOE)DE-FG36-93CH10581
NSFCHE 95-22179
NSFASC 92-100368
Chevron Petroleum Technology Co.UNSPECIFIED
Chevron Chemical CompanyUNSPECIFIED
Chevron Research and Technology Co.UNSPECIFIED
Avery- DennisonUNSPECIFIED
Caltech Beckman InstituteUNSPECIFIED
Issue or Number:8
PubMed Central ID:PMC22479
Record Number:CaltechAUTHORS:20141126-100859547
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Official Citation:Brameld, K. A., & Goddard, W. A. (1998). The role of enzyme distortion in the single displacement mechanism of family 19 chitinases. Proceedings of the National Academy of Sciences, 95(8), 4276-4281.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:52175
Deposited On:26 Nov 2014 19:23
Last Modified:10 Nov 2021 19:22

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