4wmi

Crystal structure of mouse Xyloside xylosyltransferase 1 complexed with manganese, product ligand and UDP (Product complex I)

spinqualitylabelsall models 4wmi, resolution 1.87Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4wmi is a 2 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.87Å Ligands: BGC, MN, SO4, UDP, XYS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function XXLT1_MOUSE Alpha-1,3-xylosyltransferase, which elongates the O-linked xylose-glucose disaccharide attached to EGF-like repeats in the extracellular domain of Notch proteins by catalyzing the addition of the second xylose. Publication Abstract from PubMed A major question remaining in glycobiology is how a glycosyltransferase (GT) that retains the anomeric linkage of a sugar catalyzes the reaction. Xyloside alpha-1,3-xylosyltransferase (XXYLT1) is a retaining GT that regulates Notch receptor activation by adding xylose to the Notch extracellular domain. Here, using natural acceptor and donor substrates and active Mus musculus XXYLT1, we report a series of crystallographic snapshots along the reaction, including an unprecedented natural and competent Michaelis reaction complex for retaining enzymes. These structures strongly support the SNi-like reaction as the retaining mechanism for XXYLT1. Unexpectedly, the epidermal growth factor-like repeat acceptor substrate undergoes a large conformational change upon binding to the active site, providing a structural basis for substrate specificity. Our improved understanding of this retaining enzyme will accelerate the design of retaining GT inhibitors that can modulate Notch activity in pathological situations in which Notch dysregulation is known to cause cancer or developmental disorders. Notch-modifying xylosyltransferase structures support an SNi-like retaining mechanism.,Yu H, Takeuchi M, LeBarron J, Kantharia J, London E, Bakker H, Haltiwanger RS, Li H, Takeuchi H Nat Chem Biol. 2015 Nov;11(11):847-54. doi: 10.1038/nchembio.1927. Epub 2015 Sep , 28. PMID:26414444 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Factor IX 3D structures

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