4lw3 | pdb_00004lw3

Crystal structure of the Drosophila beta1,4galactosyltransferase7 catalytic domain D211N single mutant enzyme complex with manganese and UDP-galactose

spinqualitylabelsall models 4lw3, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4lw3 is a 1 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2Å Ligands: GDU, MN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B4GT7_DROME Transfers galactose from UDP-D-Galactose (UDP-Gal) to the acceptor xylose residue in the linkage tetrasaccharide region of the glycosaminoglycan side chain of proteoglycans (PubMed:12215432, PubMed:12244071, PubMed:12590131, PubMed:20236943). No activity towards beta-GlcNAc, beta-Glc, beta-Gal, and beta-GalNAc as acceptors (PubMed:12244071, PubMed:12590131). 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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