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Crystal structure of TDP-fucosamine acetyltransferase (WecD)- complex with acetyl-CoA

Overview

Enterobacterial common antigen (ECA) is a polysaccharide found on the, outer membrane of virtually all gram-negative enteric bacteria and, consists of three sugars, N-acetyl-d-glucosamine, N-acetyl-d-mannosaminuronic acid, and 4-acetamido-4,6-dideoxy-d-galactose, organized into trisaccharide repeating units having the sequence, -->3)-alpha-d-Fuc4NAc-(1-->4)-beta-d-ManNAcA-(1-->4)-alpha-d-GlcNAc-(1-->., While the precise function of ECA is unknown, it has been linked to the, resistance of Shiga-toxin-producing Escherichia coli (STEC) O157:H7 to, organic acids and the resistance of Salmonella enterica to bile salts. The, final step in the synthesis of 4-acetamido-4,6-dideoxy-d-galactose, the, acetyl-coenzyme A (CoA)-dependent acetylation of the 4-amino group, is, carried out by TDP-fucosamine acetyltransferase (WecD). We have determined, the crystal structure of WecD in apo form at a 1.95-Angstrom resolution, and bound to acetyl-CoA at a 1.66-Angstrom resolution. WecD is a dimeric, enzyme, with each monomer adopting the GNAT N-acetyltransferase fold, common to a number of enzymes involved in acetylation of histones, aminoglycoside antibiotics, serotonin, and sugars. The crystal structure, of WecD, however, represents the first structure of a GNAT family member, that acts on nucleotide sugars. Based on this cocrystal structure, we have, used flexible docking to generate a WecD-bound model of the, acetyl-CoA-TDP-fucosamine tetrahedral intermediate, representing the, structure during acetyl transfer. Our structural data show that WecD does, not possess a residue that directly functions as a catalytic base, although Tyr208 is well positioned to function as a general acid by, protonating the thiolate anion of coenzyme A.

About this Structure

2FT0 is a Single protein structure of sequence from Escherichia coli with as ligand. Full crystallographic information is available from OCA.

Reference

Crystal structure of TDP-fucosamine acetyltransferase (WecD) from Escherichia coli, an enzyme required for enterobacterial common antigen synthesis., Hung MN, Rangarajan E, Munger C, Nadeau G, Sulea T, Matte A, J Bacteriol. 2006 Aug;188(15):5606-17. PMID:16855251

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