4wn2
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==Crystal structure of mouse Xyloside xylosyltransferase 1 complexed with manganese, product ligand and UDP (Product complex III)== | ==Crystal structure of mouse Xyloside xylosyltransferase 1 complexed with manganese, product ligand and UDP (Product complex III)== | ||
| - | <StructureSection load='4wn2' size='340' side='right' caption='[[4wn2]], [[Resolution|resolution]] 1.95Å' scene=''> | + | <StructureSection load='4wn2' size='340' side='right'caption='[[4wn2]], [[Resolution|resolution]] 1.95Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4wn2]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WN2 OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[4wn2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WN2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WN2 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand= | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene>, <scene name='pdbligand=XYS:XYLOPYRANOSE'>XYS</scene></td></tr> | |
| - | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4wn2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wn2 OCA], [https://pdbe.org/4wn2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wn2 RCSB], [https://www.ebi.ac.uk/pdbsum/4wn2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wn2 ProSAT]</span></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | |
</table> | </table> | ||
| - | == Disease == | ||
| - | [[http://www.uniprot.org/uniprot/FA9_HUMAN FA9_HUMAN]] Defects in F9 are the cause of recessive X-linked hemophilia B (HEMB) [MIM:[http://omim.org/entry/306900 306900]]; also known as Christmas disease.<ref>PMID:8295821</ref> <ref>PMID:2592373</ref> <ref>PMID:2743975</ref> <ref>PMID:6603618</ref> <ref>PMID:3009023</ref> <ref>PMID:3790720</ref> <ref>PMID:3401602</ref> <ref>PMID:3243764</ref> <ref>PMID:2713493</ref> <ref>PMID:2714791</ref> <ref>PMID:2773937</ref> <ref>PMID:2775660</ref> <ref>PMID:2753873</ref> <ref>PMID:2738071</ref> <ref>PMID:2472424</ref> <ref>PMID:2339358</ref> <ref>PMID:2372509</ref> <ref>PMID:2162822</ref> <ref>PMID:1958666</ref> <ref>PMID:1902289</ref> <ref>PMID:1346975</ref> <ref>PMID:1615485</ref> <ref>PMID:8257988</ref> <ref>PMID:8076946</ref> <ref>PMID:8199596</ref> <ref>PMID:7981722</ref> <ref>PMID:8680410</ref> <ref>PMID:9222764</ref> <ref>PMID:9590153</ref> <ref>PMID:9452115</ref> <ref>PMID:9600455</ref> <ref>PMID:10698280</ref> <ref>PMID:10094553</ref> <ref>PMID:11122099</ref> <ref>PMID:12588353</ref> <ref>PMID:12604421</ref> Note=Mutations in position 43 (Oxford-3, San Dimas) and 46 (Cambridge) prevents cleavage of the propeptide, mutation in position 93 (Alabama) probably fails to bind to cell membranes, mutation in position 191 (Chapel-Hill) or in position 226 (Nagoya OR Hilo) prevent cleavage of the activation peptide. Defects in F9 are the cause of thrombophilia due to factor IX defect (THPH8) [MIM:[http://omim.org/entry/300807 300807]]. A hemostatic disorder characterized by a tendency to thrombosis.<ref>PMID:19846852</ref> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/XXLT1_MOUSE 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. |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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. | ||
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| + | 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<ref>PMID:26414444</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4wn2" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Factor IX 3D structures|Factor IX 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Homo sapiens]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Mus musculus]] |
| - | [[Category: | + | [[Category: Li H]] |
| - | [[Category: | + | [[Category: Yu H]] |
Current revision
Crystal structure of mouse Xyloside xylosyltransferase 1 complexed with manganese, product ligand and UDP (Product complex III)
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