1oi6
From Proteopedia
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STRUCTURE DETERMINATION OF THE TMP-COMPLEX OF EVAD
Overview
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 A 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.
About this Structure
1OI6 is a Single protein structure of sequence from Amycolatopsis orientalis with TMP and GOL as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
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., Merkel AB, Major LL, Errey JC, Burkart MD, Field RA, Walsh CT, Naismith JH, J Biol Chem. 2004 Jul 30;279(31):32684-91. Epub 2004 May 24. PMID:15159413
Page seeded by OCA on Tue Dec 18 17:44:52 2007
