4gll | pdb_00004gll

Crystal structure of human UDP-xylose synthase.

spinqualitylabelsall models 4gll, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4gll is a 2 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 4ef7. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GAI, NAD, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function UXS1_HUMAN Catalyzes the NAD-dependent decarboxylation of UDP-glucuronic acid to UDP-xylose. Necessary for the biosynthesis of the core tetrasaccharide in glycosaminoglycan biosynthesis. Publication Abstract from PubMed Human UDP-alpha-d-xylose synthase (hUXS) is a member of the short-chain dehydrogenase/reductase family of nucleotide-sugar modifying enzymes. hUXS contains a bound NAD(+) cofactor that it recycles by first oxidizing UDP-alpha-d-glucuronic acid (UGA), and then reducing the UDP-alpha-d-4-keto-xylose (UX4O) to produce UDP-alpha-d-xylose (UDX). Despite the observation that purified hUXS contains a bound cofactor, it has been reported that exogenous NAD(+) will stimulate enzyme activity. Here we show that a small fraction of hUXS releases the NADH and UX4O intermediates as products during turnover. The resulting apoenzyme can be rescued by exogenous NAD(+), explaining the apparent stimulatory effect of added cofactor. The slow release of NADH and UX4O as side products by hUXS is reminiscent of the Escherichia coli UGA decarboxylase (ArnA), a related enzyme that produces NADH and UX4O as products. We report that ArnA can rebind NADH and UX4O to slowly make UDX. This means that both enzymes share the same catalytic machinery, but differ in the preferred final product. We present a bifurcated rate equation that explains how the substrate is shunted to the distinct final products. Using a new crystal structure of hUXS, we identify the structural elements of the shunt and propose that the local unfolding of the active site directs reactants toward the preferred products. Finally, we present evidence that the release of NADH and UX4O involves a cooperative conformational change that is conserved in both enzymes. Human UDP-alpha-d-xylose Synthase and Escherichia coli ArnA Conserve a Conformational Shunt That Controls Whether Xylose or 4-Keto-Xylose Is Produced.,Polizzi SJ, Walsh RM Jr, Peeples WB, Lim JM, Wells L, Wood ZA Biochemistry. 2012 Nov 6;51(44):8844-55. doi: 10.1021/bi301135b. Epub 2012 Oct, 29. PMID:23072385 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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