1oi6
From Proteopedia
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. 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 Sat May 3 03:52:36 2008
