6om8 | pdb_00006om8

Caenorhabditis Elegans UDP-Glucose Dehydrogenase in complex with UDP-Xylose

spinqualitylabelsall models 6om8, resolution 2.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6om8 is a 12 chain structure with sequence from Caenorhabditis elegans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.449Å Ligands: UDX Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function UGDH_CAEEL Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate. Publication Abstract from PubMed Human UDP-glucose dehydrogenase (hUGDH) oxidizes uridine diphosphate (UDP)-glucose to UDP-glucuronic acid, an essential substrate in the phase II metabolism of drugs. The activity of hUGDH is controlled by an atypical allosteric mechanism in which the feedback inhibitor UDP-xylose competes with the substrate for the active site and triggers a buried allosteric switch to produce an inactive complex (E(Omega)). Previous comparisons with a nonallosteric UGDH identified six large-to-small substitutions that produce packing defects in the protein core and provide the conformational flexibility necessary for the allosteric transition. Here, we test the hypothesis that these large-to-small substitutions form a motif that can be used to identify allosteric UGDHs. Caenorhabditis elegans UGDH (cUGDH) conserves this motif with the exception of an Ala-to-Pro substitution in position 109. The crystal structures of unliganded and UDP-xylose bound cUGDH show that the A109P substitution is accommodated by an Asn-to-Ser substitution at position 290. Steady-state analysis and sedimentation velocity studies show that the allosteric transition is conserved in cUGDH. The enzyme also exhibits hysteresis in progress curves and negative cooperativity with respect to NAD(+) binding. Both of these phenomena are conserved in the human enzyme, which is strong evidence that these represent fundamental features of atypical allostery in UGDH. A phylogenetic analysis of UGDH shows that the atypical allostery motif is ancient and identifies a potential transition point in the evolution of the UGDH family. Conservation of Atypical Allostery in C. elegans UDP-Glucose Dehydrogenase.,Beattie NR, Keul ND, Hicks Sirmans TN, McDonald WE, Talmadge TM, Taujale R, Kannan N, Wood ZA ACS Omega. 2019 Sep 24;4(15):16318-16329. doi: 10.1021/acsomega.9b01565., eCollection 2019 Oct 8. PMID:31616809 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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