This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

5mri

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 07:26, 19 August 2020

Crystal structure of the Vps10p domain of human sortilin/NTS3 in complex with Triazolone 18

Structural highlights

5mri is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Gene:	SORT1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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

[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.^[1] ^[2] ^[3] ^[4] ^[5] ^[6] ^[7] ^[8] ^[9] ^[10]

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^[11]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Nielsen MS, Jacobsen C, Olivecrona G, Gliemann J, Petersen CM. Sortilin/neurotensin receptor-3 binds and mediates degradation of lipoprotein lipase. J Biol Chem. 1999 Mar 26;274(13):8832-6. PMID:10085125
↑ Nielsen MS, Madsen P, Christensen EI, Nykjaer A, Gliemann J, Kasper D, Pohlmann R, Petersen CM. The sortilin cytoplasmic tail conveys Golgi-endosome transport and binds the VHS domain of the GGA2 sorting protein. EMBO J. 2001 May 1;20(9):2180-90. PMID:11331584 doi:10.1093/emboj/20.9.2180
↑ Takatsu H, Katoh Y, Shiba Y, Nakayama K. Golgi-localizing, gamma-adaptin ear homology domain, ADP-ribosylation factor-binding (GGA) proteins interact with acidic dileucine sequences within the cytoplasmic domains of sorting receptors through their Vps27p/Hrs/STAM (VHS) domains. J Biol Chem. 2001 Jul 27;276(30):28541-5. Epub 2001 Jun 4. PMID:11390366 doi:10.1074/jbc.C100218200
↑ Maeda S, Nobukuni T, Shimo-Onoda K, Hayashi K, Yone K, Komiya S, Inoue I. Sortilin is upregulated during osteoblastic differentiation of mesenchymal stem cells and promotes extracellular matrix mineralization. J Cell Physiol. 2002 Oct;193(1):73-9. PMID:12209882 doi:10.1002/jcp.10151
↑ Lefrancois S, Zeng J, Hassan AJ, Canuel M, Morales CR. The lysosomal trafficking of sphingolipid activator proteins (SAPs) is mediated by sortilin. EMBO J. 2003 Dec 15;22(24):6430-7. PMID:14657016 doi:10.1093/emboj/cdg629
↑ Martin S, Vincent JP, Mazella J. Involvement of the neurotensin receptor-3 in the neurotensin-induced migration of human microglia. J Neurosci. 2003 Feb 15;23(4):1198-205. PMID:12598608
↑ Morinville A, Martin S, Lavallee M, Vincent JP, Beaudet A, Mazella J. Internalization and trafficking of neurotensin via NTS3 receptors in HT29 cells. Int J Biochem Cell Biol. 2004 Nov;36(11):2153-68. PMID:15313463 doi:10.1016/j.biocel.2004.04.013
↑ Nykjaer A, Lee R, Teng KK, Jansen P, Madsen P, Nielsen MS, Jacobsen C, Kliemannel M, Schwarz E, Willnow TE, Hempstead BL, Petersen CM. Sortilin is essential for proNGF-induced neuronal cell death. Nature. 2004 Feb 26;427(6977):843-8. PMID:14985763 doi:10.1038/nature02319
↑ Teng HK, Teng KK, Lee R, Wright S, Tevar S, Almeida RD, Kermani P, Torkin R, Chen ZY, Lee FS, Kraemer RT, Nykjaer A, Hempstead BL. ProBDNF induces neuronal apoptosis via activation of a receptor complex of p75NTR and sortilin. J Neurosci. 2005 Jun 1;25(22):5455-63. PMID:15930396 doi:25/22/5455
↑ Chen ZY, Ieraci A, Teng H, Dall H, Meng CX, Herrera DG, Nykjaer A, Hempstead BL, Lee FS. Sortilin controls intracellular sorting of brain-derived neurotrophic factor to the regulated secretory pathway. J Neurosci. 2005 Jun 29;25(26):6156-66. PMID:15987945 doi:25/26/6156
↑ Andersen JL, Lindberg S, Langgard M, Maltas PJ, Ronn LCB, Bundgaard C, Strandbygaard D, Thirup S, Watson SP. The identification of novel acid isostere based inhibitors of the VPS10P family sorting receptor Sortilin. 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 doi:http://dx.doi.org/10.1016/j.bmcl.2017.02.028

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5mri"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the Vps10p domain of human sortilin/NTS3 in complex with Triazolone 18==
-<StructureSection load='5mri' size='340' side='right' caption='[[5mri]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
+<StructureSection load='5mri' size='340' side='right'caption='[[5mri]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5mri]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MRI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MRI FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5mri]] 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=5MRI OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5MRI FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Q9Y:~{N}-METHYL-3-(3-METHYLBUTYL)-5-OXIDANYL-1,2,3-TRIAZOLE-4-CARBOXAMIDE'>Q9Y</scene></td></tr>
+</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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Q9Y:~{N}-METHYL-3-(3-METHYLBUTYL)-5-OXIDANYL-1,2,3-TRIAZOLE-4-CARBOXAMIDE'>Q9Y</scene></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=5mri FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mri OCA], [http://pdbe.org/5mri PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mri RCSB], [http://www.ebi.ac.uk/pdbsum/5mri PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mri ProSAT]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SORT1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5mri FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mri OCA], [http://pdbe.org/5mri PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mri RCSB], [http://www.ebi.ac.uk/pdbsum/5mri PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mri ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 27: / Line 28: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Andersen, J L]]
 [[Category: Strandbygaard, D]]

5mri

From Proteopedia

Revision as of 07:26, 19 August 2020

Crystal structure of the Vps10p domain of human sortilin/NTS3 in complex with Triazolone 18

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox