4bc4

Crystal structure of human D-xylulokinase in complex with D-xylulose

spinqualitylabelsall models 4bc4, resolution 1.79Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4bc4 is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: EDO, MSE, XUL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function XYLB_HUMAN Phosphorylates D-xylulose to produce D-xylulose 5-phosphate, a molecule that may play an important role in the regulation of glucose metabolism and lipogenesis. Publication Abstract from PubMed D-Xylulokinase (XK; EC 2.7.1.17) catalyzes the ATP-dependent phosphorylation of D-xylulose (Xu) to produce xylulose-5-phosphate (Xu5P). In mammals, XK is the last enzyme in the glucuronate-xylulose pathway, active in the liver and kidneys, and is linked through its product Xu5P to the pentose phosphate pathway. XK may play an important role in metabolic disease, given that Xu5P is a key regulator of glucose metabolism and lipogenesis. We have expressed the product of a putative human XK gene, and identified it as the authentic human D-xylulokinase (hXK). NMR studies with a variety of sugars showed that hXK acts only on D-xylulose, and a coupled photometric assay established its key kinetic parameters as KM(Xu) = 24 +/- 3 muM and kcat = 35 +/- 5 s-1. Crystal structures were determined for hXK, on its own and in complexes with Xu, ADP and a fluorinated inhibitor. These reveal that hXK has two-domain fold characteristic of the sugar kinase/hsp70/actin superfamily, with glycerol kinase as its closest relative. Xu binds to domain-I and ADP to domain-II, but in this open form of hXK they are 10 A apart, implying that a large-scale conformational change is required for catalysis. Xu binds in its linear keto form, sandwiched between a Trp side chain and polar side chains that provide exquisite hydrogen bonding recognition. The hXK structure provides a basis for the design of specific inhibitors with which to probe its roles in sugar metabolism and metabolic disease. Structure and function of human xylulokinase, an enzyme with important roles in carbohydrate metabolism.,Bunker RD, Bulloch EM, Dickson JM, Loomes KM, Baker EN J Biol Chem. 2012 Nov 23. PMID:23179721 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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