View source for 4uz9


==STRUCTURE OF THE WNT DEACYLASE NOTUM - CRYSTAL FORM VII - SOS COMPLEX - 2.2A==
<StructureSection load='4uz9' size='340' side='right'caption='[[4uz9]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4uz9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4UZ9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4UZ9 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SCR:SUCROSE+OCTASULFATE'>SCR</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4uyu|4uyu]], [[4uyw|4uyw]], [[4uyz|4uyz]], [[4uz1|4uz1]], [[4uz5|4uz5]], [[4uz6|4uz6]], [[4uz7|4uz7]], [[4uza|4uza]], [[4uzj|4uzj]], [[4uzk|4uzk]], [[4uzl|4uzl]], [[4uzq|4uzq]], [[4wbh|4wbh]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Carboxylesterase Carboxylesterase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.1.1 3.1.1.1] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4uz9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4uz9 OCA], [http://pdbe.org/4uz9 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4uz9 RCSB], [http://www.ebi.ac.uk/pdbsum/4uz9 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4uz9 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4uz9" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Carboxylesterase]]
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Jones, E Y]]
[[Category: Zebisch, M]]
[[Category: Alpha/beta hydrolase]]
[[Category: Esterase]]
[[Category: Extracellular]]
[[Category: Hydrolase]]
[[Category: Wnt]]