1hzj

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Revision as of 15:18, 12 November 2007

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spinqualitylabelsall models 1hzj, resolution 1.5Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

HUMAN UDP-GALACTOSE 4-EPIMERASE: ACCOMMODATION OF UDP-N-ACETYLGLUCOSAMINE WITHIN THE ACTIVE SITE

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

UDP-galactose 4-epimerase catalyzes the interconversion of UDP-galactose, and UDP-glucose during normal galactose metabolism. One of the key, structural features in the proposed reaction mechanism for the enzyme is, the rotation of a 4'-ketopyranose intermediate within the active site, pocket. Recently, the three-dimensional structure of the human enzyme with, bound NADH and UDP-glucose was determined. Unlike that observed for the, protein isolated from Escherichia coli, the human enzyme can also turn, over UDP-GlcNAc to UDP-GalNAc and vice versa. Here we describe the, three-dimensional structure of human epimerase complexed with NADH and, UDP-GlcNAc. To accommodate the additional N-acetyl group at the C2, position of the sugar, the side chain of Asn-207 rotates toward the, interior of the protein and interacts with Glu-199. Strikingly, in the, human enzyme, the structural equivalent of Tyr-299 in the E. coli protein, is replaced with a cysteine residue (Cys-307) and the active site volume, for the human protein is calculated to be approximately 15% larger than, that observed for the bacterial epimerase. This combination of a larger, active site cavity and amino acid residue replacement most likely accounts, for the inability of the E. coli enzyme to interconvert UDP-GlcNAc and, UDP-GalNAc.

Disease

Known disease associated with this structure: Galactose epimerase deficiency OMIM:[606953]

About this Structure

1HZJ is a Single protein structure of sequence from Homo sapiens with CL, MG, NAD and UD1 as ligands. Active as UDP-glucose 4-epimerase, with EC number 5.1.3.2 Full crystallographic information is available from OCA.

Reference

Human UDP-galactose 4-epimerase. Accommodation of UDP-N-acetylglucosamine within the active site., Thoden JB, Wohlers TM, Fridovich-Keil JL, Holden HM, J Biol Chem. 2001 May 4;276(18):15131-6. Epub 2001 Jan 26. PMID:11279032

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