4uz5: Difference between revisions
New page: '''Unreleased structure''' The entry 4uz5 is ON HOLD Authors: Zebisch, M., Jones, E.Y. Description: Structure of a Wnt Signal regulator -crystal form IV -2.1A |
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==STRUCTURE OF THE WNT DEACYLASE NOTUM - CRYSTAL FORM IV - 2.1A== | |||
<StructureSection load='4uz5' size='340' side='right'caption='[[4uz5]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4uz5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UZ5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4UZ5 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]] 2.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=4uz5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uz5 OCA], [https://pdbe.org/4uz5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4uz5 RCSB], [https://www.ebi.ac.uk/pdbsum/4uz5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4uz5 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/NOTUM_HUMAN NOTUM_HUMAN] May deacetylate GlcNAc residues on cell surface glycans. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Signalling by Wnt proteins is finely balanced to ensure normal development and tissue homeostasis while avoiding diseases such as cancer. This is achieved in part by Notum, a highly conserved secreted feedback antagonist. Notum has been thought to act as a phospholipase, shedding glypicans and associated Wnt proteins from the cell surface. However, this view fails to explain specificity, as glypicans bind many extracellular ligands. Here we provide genetic evidence in Drosophila that Notum requires glypicans to suppress Wnt signalling, but does not cleave their glycophosphatidylinositol anchor. Structural analyses reveal glycosaminoglycan binding sites on Notum, which probably help Notum to co-localize with Wnt proteins. They also identify, at the active site of human and Drosophila Notum, a large hydrophobic pocket that accommodates palmitoleate. Kinetic and mass spectrometric analyses of human proteins show that Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnt proteins and thus constitutes the first known extracellular protein deacylase. | |||
Notum deacylates Wnt proteins to suppress signalling activity.,Kakugawa S, Langton PF, Zebisch M, Howell SA, Chang TH, Liu Y, Feizi T, Bineva G, O'Reilly N, Snijders AP, Jones EY, Vincent JP Nature. 2015 Mar 12;519(7542):187-92. doi: 10.1038/nature14259. Epub 2015 Feb 25. PMID:25731175<ref>PMID:25731175</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4uz5" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Jones EY]] | |||
[[Category: Zebisch M]] | |||
Latest revision as of 06:36, 21 November 2024
STRUCTURE OF THE WNT DEACYLASE NOTUM - CRYSTAL FORM IV - 2.1ASTRUCTURE OF THE WNT DEACYLASE NOTUM - CRYSTAL FORM IV - 2.1A
Structural highlights
FunctionNOTUM_HUMAN May deacetylate GlcNAc residues on cell surface glycans. Publication Abstract from PubMedSignalling by Wnt proteins is finely balanced to ensure normal development and tissue homeostasis while avoiding diseases such as cancer. This is achieved in part by Notum, a highly conserved secreted feedback antagonist. Notum has been thought to act as a phospholipase, shedding glypicans and associated Wnt proteins from the cell surface. However, this view fails to explain specificity, as glypicans bind many extracellular ligands. Here we provide genetic evidence in Drosophila that Notum requires glypicans to suppress Wnt signalling, but does not cleave their glycophosphatidylinositol anchor. Structural analyses reveal glycosaminoglycan binding sites on Notum, which probably help Notum to co-localize with Wnt proteins. They also identify, at the active site of human and Drosophila Notum, a large hydrophobic pocket that accommodates palmitoleate. Kinetic and mass spectrometric analyses of human proteins show that Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnt proteins and thus constitutes the first known extracellular protein deacylase. Notum deacylates Wnt proteins to suppress signalling activity.,Kakugawa S, Langton PF, Zebisch M, Howell SA, Chang TH, Liu Y, Feizi T, Bineva G, O'Reilly N, Snijders AP, Jones EY, Vincent JP Nature. 2015 Mar 12;519(7542):187-92. doi: 10.1038/nature14259. Epub 2015 Feb 25. PMID:25731175[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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