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Merkel, Alexandra B., Major, Louise L., Errey, James C., Burkart, Michael D., Field, Robert A. 
ORCID: https://orcid.org/0000-0001-8574-0275, Walsh, Christopher T. and Naismith, James H.
(2004)
The position of a key tyrosine in dTDP-4-keto-6-deoxy-D-glucose-5-epimerase (EvaD) alters the substrate profile for this RmlC-like enzyme.
Journal of Biological Chemistry, 279 (31).
pp. 32684-32691.
ISSN 0021-9258
Abstract
Vancomycin, the last line of defense antibiotic, depends upon the attachment of the carbohydrate vancosamine to an aglycone skeleton for antibacterial activity. Vancomycin is a naturally occurring secondary metabolite that can be produced by bacterial fermentation. To combat emerging resistance, it has been proposed to genetically engineer bacteria to produce analogues of vancomycin. This requires a detailed understanding of the biochemical steps in the synthesis of vancomycin. Here we report the 1.4 Å structure and biochemical characterization of EvaD, an RmlC-like protein that is required for the C-5′ epimerization during synthesis of dTDP-epivancosamine. EvaD, although clearly belonging to the RmlC class of enzymes, displays very low activity in the archetypal RmlC reaction (double epimerization of dTDP-6-deoxy-4-keto-D-glucose at C-3′ and C-5′). The high resolution structure of EvaD compared with the structures of authentic RmlC enzymes indicates that a subtle change in the enzyme active site repositions a key catalytic Tyr residue. A mutant designed to re-establish the normal position of the Tyr increases the RmlC-like activity of EvaD.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | biochemistry,molecular biology,cell biology ,/dk/atira/pure/subjectarea/asjc/1300/1303 |
| Faculty \ School: | Faculty of Science > School of Chemistry, Pharmacy and Pharmacology |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 10 Sep 2024 12:30 |
| Last Modified: | 25 Sep 2024 18:08 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/96647 |
| DOI: | 10.1074/jbc.M404091200 |
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