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The Structure of the UDP-Glc/GlcNAc 4-Epimerase from the Human Pathogen Campylobacter jejuni

Yun, Hyun Gi and Jang, Kyoung-Soon and Tanaka, Shiho and Clemons, William M., Jr. (2016) The Structure of the UDP-Glc/GlcNAc 4-Epimerase from the Human Pathogen Campylobacter jejuni. Glycobiology, 26 (12). p. 1404. ISSN 0959-6658. doi:10.1093/glycob/cww110.

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Worldwide, the food-born pathogen Campylobacter jejuni is the leading bacterial source of human gastroenteritis. C. jejuni produces a large number of atypical cell-surface carbohydrates that facilitate infections. A major component of these oligo- and polysaccharides is the sugar N-acetylgalactosamine (GalNAc). The sole source of this critical sugar is derived by the epimerization of UDP-N-acetylglucosamine (GlcNAc) catalyzed by the enzyme UDP-GlcNAc 4-epimerase (GNE). This enzyme is unique among known bacterial epimerases in that it also catalyzes the equivalent reaction with the non-N-acetylated sugars. Understanding how CjGNE catalyzes these various interconversions is critical to designing novel inhibitors of this enzyme. Here, to further the mechanistic understanding we present a 2.0Å crystal structure of CjGNE with its NAD+ co-factor bound. Based on novel features found in the structure we perform a variety of biochemical studies to probe the mechanism and compare these results to the only other structurally characterized bi-functional epimerase, the human homolog GalE. We further show that ebselen, previously identified for inhibition of HsGalE, is active against CjGNE, suggesting a route for antibiotic development.

Item Type:Article
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URLURL TypeDescription ItemDiscussion Paper - September 22, 2020
Clemons, William M., Jr.0000-0002-0021-889X
Additional Information:© 2016 The Author. Published by Oxford University Press. Published: 05 December 2016.
Issue or Number:12
Record Number:CaltechAUTHORS:20170224-084058196
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:74521
Deposited By: Tony Diaz
Deposited On:24 Feb 2017 18:03
Last Modified:11 Nov 2021 05:27

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