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| | <StructureSection load='1nz7' size='340' side='right'caption='[[1nz7]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='1nz7' size='340' side='right'caption='[[1nz7]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1nz7]] 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=1NZ7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1NZ7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1nz7]] 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=1NZ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NZ7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=901:2-[(4-{2-ACETYLAMINO-2-[4-(1-CARBOXY-3-METHYLSULFANYL-PROPYLCARBAMOYL)-BUTYLCARBAMOYL]-ETHYL}-2-ETHYL-PHENYL)-OXALYL-AMINO]-BENZOIC+ACID'>901</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1nl9|1nl9]], [[1nny|1nny]], [[1no6|1no6]], [[1ony|1ony]], [[1onz|1onz]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=901:2-[(4-{2-ACETYLAMINO-2-[4-(1-CARBOXY-3-METHYLSULFANYL-PROPYLCARBAMOYL)-BUTYLCARBAMOYL]-ETHYL}-2-ETHYL-PHENYL)-OXALYL-AMINO]-BENZOIC+ACID'>901</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPN1 OR PTP1B ([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'>[https://proteopedia.org/fgij/fg.htm?mol=1nz7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nz7 OCA], [https://pdbe.org/1nz7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nz7 RCSB], [https://www.ebi.ac.uk/pdbsum/1nz7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nz7 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </span></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=1nz7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nz7 OCA], [http://pdbe.org/1nz7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1nz7 RCSB], [http://www.ebi.ac.uk/pdbsum/1nz7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1nz7 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PTN1_HUMAN PTN1_HUMAN]] Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion.<ref>PMID:21135139</ref> <ref>PMID:22169477</ref> | + | [https://www.uniprot.org/uniprot/PTN1_HUMAN PTN1_HUMAN] Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion.<ref>PMID:21135139</ref> <ref>PMID:22169477</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Protein-tyrosine-phosphatase]]
| + | [[Category: Abad-Zapatero C]] |
| - | [[Category: Abad-Zapatero, C]] | + | [[Category: Ballaron SJ]] |
| - | [[Category: Ballaron, S J]] | + | [[Category: Hajduk PJ]] |
| - | [[Category: Hajduk, P J]] | + | [[Category: Hutchins CW]] |
| - | [[Category: Hutchins, C W]] | + | [[Category: Jirousek MR]] |
| - | [[Category: Jirousek, M R]] | + | [[Category: Liu G]] |
| - | [[Category: Liu, G]] | + | [[Category: Lubben T]] |
| - | [[Category: Lubben, T]] | + | [[Category: Oost TK]] |
| - | [[Category: Oost, T K]] | + | [[Category: Pei Z]] |
| - | [[Category: Pei, Z]] | + | [[Category: Stashko MA]] |
| - | [[Category: Stashko, M A]] | + | [[Category: Szczepankiewicz BG]] |
| - | [[Category: Szczepankiewicz, B G]] | + | [[Category: Trevillyan JM]] |
| - | [[Category: Trevillyan, J M]] | + | [[Category: Xin Z]] |
| - | [[Category: Xin, Z]] | + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Oxamic acid inhibitor bound to p-loop]]
| + | |
| - | [[Category: Protein tyrosine phosphatase fold]]
| + | |
| Structural highlights
Function
PTN1_HUMAN Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
We have previously reported a novel series of oxalyl-aryl-amino benzoic acid-based, catalytic site-directed, competitive, reversible protein tyrosine phosphatase 1B (PTP1B) inhibitors. With readily access to key intermediates, we utilized a solution phase parallel synthesis approach and rapidly identified a highly potent PTP1B inhibitor (19, K(i)=76 nM) with moderate selectivity (5-fold) over T-cell PTPase (TCPTP) through interacting with a second phosphotyrosine binding site (site 2) in the close proximity to the catalytic site.
Potent, selective inhibitors of protein tyrosine phosphatase 1B.,Xin Z, Oost TK, Abad-Zapatero C, Hajduk PJ, Pei Z, Szczepankiewicz BG, Hutchins CW, Ballaron SJ, Stashko MA, Lubben T, Trevillyan JM, Jirousek MR, Liu G Bioorg Med Chem Lett. 2003 Jun 2;13(11):1887-90. PMID:12749891[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nievergall E, Janes PW, Stegmayer C, Vail ME, Haj FG, Teng SW, Neel BG, Bastiaens PI, Lackmann M. PTP1B regulates Eph receptor function and trafficking. J Cell Biol. 2010 Dec 13;191(6):1189-203. doi: 10.1083/jcb.201005035. Epub 2010, Dec 6. PMID:21135139 doi:10.1083/jcb.201005035
- ↑ Krishnan N, Fu C, Pappin DJ, Tonks NK. H2S-Induced sulfhydration of the phosphatase PTP1B and its role in the endoplasmic reticulum stress response. Sci Signal. 2011 Dec 13;4(203):ra86. doi: 10.1126/scisignal.2002329. PMID:22169477 doi:10.1126/scisignal.2002329
- ↑ Xin Z, Oost TK, Abad-Zapatero C, Hajduk PJ, Pei Z, Szczepankiewicz BG, Hutchins CW, Ballaron SJ, Stashko MA, Lubben T, Trevillyan JM, Jirousek MR, Liu G. Potent, selective inhibitors of protein tyrosine phosphatase 1B. Bioorg Med Chem Lett. 2003 Jun 2;13(11):1887-90. PMID:12749891
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