4irq

Crystal structure of catalytic domain of human beta1,4galactosyltransferase 7 in closed conformation in complex with manganese and UDP

spinqualitylabelsall models 4irq, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4irq is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.3Å Ligands: MN, TRS, UDP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease B4GT7_HUMAN Ehlers-Danlos syndrome, progeroid type. The disease is caused by mutations affecting the gene represented in this entry. Function B4GT7_HUMAN Required for the biosynthesis of the tetrasaccharide linkage region of proteoglycans, especially for small proteoglycans in skin fibroblasts. Publication Abstract from PubMed The beta-1,4-galactosyltransferase 7 (beta4GalT7) enzyme is involved in proteoglycan synthesis. In the presence of a manganese ion, it transfers galactose from UDP-galactose to xylose on a proteoglycan acceptor substrate. We present here the crystal structures of human beta4GalT7 in open and closed conformations. A comparison of these crystal structures shows that, upon manganese and UDP or UDP-Gal binding, the enzyme undergoes conformational changes involving a small and a long loop. We also present the crystal structures of Drosophila wild-type beta4GalT7 and D211N beta4GalT7 mutant enzymes in the closed conformation in the presence of the acceptor substrate xylobiose and the donor substrate UDP-Gal, respectively. To understand the catalytic mechanism, we have crystallized the ternary complex of D211N beta4GalT7 mutant enzyme in the presence of manganese with the donor and the acceptor substrates together in the same crystal structure. The galactose moiety of the bound UDP-Gal molecule forms seven hydrogen bonds with the protein molecule. The nonreducing end of the xylose moiety of xylobiose binds to the hydrophobic acceptor sugar binding pocket created by the conformational changes, whereas its extended xylose moiety forms hydrophobic interactions with a Tyr residue. In the ternary complex crystal structure, the nucleophile O4 oxygen atom of the xylose molecule is found in close proximity to the C1 and O5 atoms of the galactose moiety. This is the first time that a Michaelis complex of a glycosyltransferase has been described, and it clearly suggests an SN2 type catalytic mechanism for the beta4GalT7 enzyme. Crystal Structures of beta-1,4-Galactosyltransferase 7 Enzyme Reveal Conformational Changes and Substrate Binding.,Tsutsui Y, Ramakrishnan B, Qasba PK J Biol Chem. 2013 Nov 1;288(44):31963-70. doi: 10.1074/jbc.M113.509984. Epub 2013, Sep 19. PMID:24052259 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Glycosyltransferase 3D structures

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