View source for 5mrh


==Crystal structure of the Vps10p domain of human sortilin/NTS3 in complex with Triazolone 1==
<StructureSection load='5mrh' size='340' side='right'caption='[[5mrh]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mrh]] 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=5MRH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MRH 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]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene>, <scene name='pdbligand=Q9Z:3-(3-METHYLBUTYL)-4~{H}-1,2,3-TRIAZOL-5-ONE'>Q9Z</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=5mrh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mrh OCA], [https://pdbe.org/5mrh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mrh RCSB], [https://www.ebi.ac.uk/pdbsum/5mrh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mrh ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SORT_HUMAN SORT_HUMAN] Note=A common polymorphism located in a non-coding region between CELSR2 and PSRC1 alters a CEBP transcription factor binding site and is responsible for changes in hepatic expression of SORT1. Altered SORT1 expression in liver affects low density lipoprotein cholesterol levels in plasma and is associated with susceptibility to myocardial infarction.
== Function ==
[https://www.uniprot.org/uniprot/SORT_HUMAN SORT_HUMAN] Functions as a sorting receptor in the Golgi compartment and as a clearance receptor on the cell surface. Required for protein transport from the Golgi apparatus to the lysosomes by a pathway that is independent of the mannose-6-phosphate receptor (M6PR). Also required for protein transport from the Golgi apparatus to the endosomes. Promotes neuronal apoptosis by mediating endocytosis of the proapoptotic precursor forms of BDNF (proBDNF) and NGFB (proNGFB). Also acts as a receptor for neurotensin. May promote mineralization of the extracellular matrix during osteogenic differentiation by scavenging extracellular LPL. Probably required in adipocytes for the formation of specialized storage vesicles containing the glucose transporter SLC2A4/GLUT4 (GLUT4 storage vesicles, or GSVs). These vesicles provide a stable pool of SLC2A4 and confer increased responsiveness to insulin. May also mediate transport from the endoplasmic reticulum to the Golgi.<ref>PMID:10085125</ref> <ref>PMID:11331584</ref> <ref>PMID:11390366</ref> <ref>PMID:12209882</ref> <ref>PMID:14657016</ref> <ref>PMID:12598608</ref> <ref>PMID:15313463</ref> <ref>PMID:14985763</ref> <ref>PMID:15930396</ref> <ref>PMID:15987945</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Using fragment based and structure based drug discovery strategies a series of novel Sortilin inhibitors has been identified. The inhibitors are based on the N-substituted 1,2,3-triazol-4-one/ol heterocyclic template. X-ray crystallography shows that the 1,2,3-triazol-4-one/ol acts as a carboxylic acid isostere, making a bi-dentate interaction with an arginine residue of Sortilin, an interaction which has not been previously characterised for this heterocycle.

The identification of novel acid isostere based inhibitors of the VPS10P family sorting receptor Sortilin.,Andersen JL, Lindberg S, Langgard M, Maltas PJ, Ronn LCB, Bundgaard C, Strandbygaard D, Thirup S, Watson SP Bioorg Med Chem Lett. 2017 Jun 1;27(11):2629-2633. doi:, 10.1016/j.bmcl.2017.02.028. Epub 2017 Feb 20. PMID:28462834<ref>PMID:28462834</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 5mrh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Neurotensin receptor|Neurotensin receptor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Andersen JL]]
[[Category: Strandbygaard D]]
[[Category: Thirup S]]