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Giraud, Marie-France, Leonard, Gordon A., Field, Robert A. 
ORCID: https://orcid.org/0000-0001-8574-0275, Berlind, Christian and Naismith, James H.
(2000)
RmIc, the third enzyme of dTDP-L-rhamnose pathway, is a new class of epimerase.
Nature Structural Biology, 7 (5).
pp. 398-402.
ISSN 1072-8368
Abstract
Deoxythymidine diphosphate (dTDP)-L-rhamnose is the precursor of L- rhamnose, a saccharide required for the virulence of some pathogenic bacteria, dTDP-L-rhamnose is synthesized from glucose-l-phosphate and deoxythymidine triphosphate (dTTP) via a pathway involving four distinct enzymes. This pathway does not exist in humans and the enzymes involved in dTDP-L-rhamnose synthesis are potential targets for the design of new therapeutic agents. Here, the crystal structure of dTDP-6-deoxy-D-xylo-4- hexulose 3,5 epimerase (RmlC, EC5.1.3.13) from Salmonella enterica serovar Typhimurium was determined. The third enzyme of the rhamnose biosynthetic pathway, RmlC epimerizes at two carbon centers, the 3 and 5 positions of the sugar ring. The structure was determined by multi-wavelength anomalous diffraction to a resolution of 2.17 Å. RmlC is a dimer and each monomer is formed mainly from two β-sheets arranged in a β-sandwich. The structure of a dTDP-phenol-RmlC complex shows the substrate-binding site to be located between the two β-sheets; this site is formed from residues of both monomers. Sequence alignments of other RmlC enzymes confirm that this region is very highly conserved. The enzyme is distinct structurally from other epimerases known and thus, is the first example of a new class of carbohydrate epimerase.
| Item Type: | Article |
|---|---|
| Additional Information: | Acknowledgements: This work was supported by the Wellcome Trust. The use of the CCLRC Daresbury Laboratory, UK, and ESRF-Grenoble facilities is gratefully acknowledged. |
| Uncontrolled Keywords: | structural biology,biochemistry,genetics ,/dk/atira/pure/subjectarea/asjc/1300/1315 |
| Faculty \ School: | Faculty of Science > School of Chemistry, Pharmacy and Pharmacology |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 11 Sep 2024 09:30 |
| Last Modified: | 25 Sep 2024 18:08 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/96688 |
| DOI: | 10.1038/75178 |
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