4wlm: Difference between revisions
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==Crystal structure of mouse Xyloside xylosyltransferase 1 complexed with manganese== | |||
<StructureSection load='4wlm' size='340' side='right'caption='[[4wlm]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4wlm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WLM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WLM FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=4wlm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wlm OCA], [https://pdbe.org/4wlm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wlm RCSB], [https://www.ebi.ac.uk/pdbsum/4wlm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wlm ProSAT]</span></td></tr> | |||
</table> | |||
== 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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4wlm" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Li H]] | |||
[[Category: Yu H]] | |||
Latest revision as of 03:54, 28 December 2023
Crystal structure of mouse Xyloside xylosyltransferase 1 complexed with manganeseCrystal structure of mouse Xyloside xylosyltransferase 1 complexed with manganese
Structural highlights
FunctionXXLT1_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 PubMedA 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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