2dkd

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2dkd, resolution 2.10Å

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Crystal structure of N-acetylglucosamine-phosphate mutase, a member of the alpha-D-phosphohexomutase superfamily, in the product complex

Overview

N-acetylglucosamine-phosphate mutase (AGM1) is an essential enzyme in the, synthetic process of UDP-N-acetylglucosamine (UDP-GlcNAc). UDP-GlcNAc is a, UDP sugar that serves as a biosynthetic precursor of glycoproteins, mucopolysaccharides, and the cell wall of bacteria. Thus, a specific, inhibitor of AGM1 from pathogenetic fungi could be a new candidate for an, antifungal reagent that inhibits cell wall synthesis. AGM1 catalyzes the, conversion of N-acetylglucosamine 6-phosphate (GlcNAc-6-P) into, N-acetylglucosamine 1-phosphate (GlcNAc-1-P). This enzyme is a member of, the alpha-D-phosphohexomutase superfamily, which catalyzes the, intramolecular phosphoryl transfer of sugar substrates. Here we report the, crystal structures of AGM1 from Candida albicans for the first time, both, in the apoform and in the complex forms with the substrate and the, product, and discuss its catalytic mechanism. The structure of AGM1, consists of four domains, of which three domains have essentially the same, fold. The overall structure is similar to those of phosphohexomutases;, however, there are two additional beta-strands in domain 4, and a circular, permutation occurs in domain 1. The catalytic cleft is formed by four, loops from each domain. The N-acetyl group of the substrate is recognized, by Val-370 and Asn-389 in domain 3, from which the substrate specificity, arises. By comparing the substrate and product complexes, it is suggested, that the substrate rotates about 180 degrees on the axis linking C-4 and, the midpoint of the C-5-O-5 bond in the reaction.

About this Structure

2DKD is a Single protein structure of sequence from Candida albicans with NG1, PO4 and ZN as ligands. Active as Phosphoacetylglucosamine mutase, with EC number 5.4.2.3 Full crystallographic information is available from OCA.

Reference

Crystal structures of N-acetylglucosamine-phosphate mutase, a member of the alpha-D-phosphohexomutase superfamily, and its substrate and product complexes., Nishitani Y, Maruyama D, Nonaka T, Kita A, Fukami TA, Mio T, Yamada-Okabe H, Yamada-Okabe T, Miki K, J Biol Chem. 2006 Jul 14;281(28):19740-7. Epub 2006 May 1. PMID:16651269

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