6x48
From Proteopedia
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==Sortilin-Progranulin Interaction With Compound 17== | ==Sortilin-Progranulin Interaction With Compound 17== | ||
| - | <StructureSection load='6x48' size='340' side='right'caption='[[6x48]]' scene=''> | + | <StructureSection load='6x48' size='340' side='right'caption='[[6x48]], [[Resolution|resolution]] 2.90Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6X48 OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6x48]] 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=6X48 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6X48 FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=UNL:UNKNOWN+LIGAND'>UNL</scene>, <scene name='pdbligand=UP4:N-(3,5-dichlorobenzene-1-carbonyl)-5,5-dimethyl-L-norleucine'>UP4</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=6x48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x48 OCA], [https://pdbe.org/6x48 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6x48 RCSB], [https://www.ebi.ac.uk/pdbsum/6x48 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6x48 ProSAT]</span></td></tr> | ||
</table> | </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 == | ||
| + | High-throughput screening methods have been used to identify two novel series of inhibitors that disrupt progranulin binding to sortilin. Exploration of structure-activity relationships (SAR) resulted in compounds with sufficient potency and physicochemical properties to enable co-crystallization with sortilin. These co-crystal structures supported observed SAR trends and provided guidance for additional avenues for designing compounds with additional interactions within the binding site. | ||
| + | |||
| + | Identification of potent inhibitors of the sortilin-progranulin interaction.,Stachel SJ, Ginnetti AT, Johnson SA, Cramer P, Wang Y, Bukhtiyarova M, Krosky D, Stump C, Hurzy DM, Schlegel KA, Cooke AJ, Allen S, O'Donnell G, Ziebell M, Parthasarathy G, Getty KL, Ho T, Ou Y, Jovanovska A, Carroll SS, Pausch M, Lumb K, Mosser SD, Voleti B, Klein DJ, Soisson SM, Zerbinatti C, Coleman PJ Bioorg Med Chem Lett. 2020 Sep 1;30(17):127403. doi: 10.1016/j.bmcl.2020.127403. , Epub 2020 Jul 15. PMID:32738972<ref>PMID:32738972</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6x48" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Neurotensin receptor|Neurotensin receptor]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Parthasarathy G]] | [[Category: Parthasarathy G]] | ||
[[Category: Soisson SM]] | [[Category: Soisson SM]] | ||
Revision as of 14:41, 18 October 2023
Sortilin-Progranulin Interaction With Compound 17
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