2b07: Difference between revisions

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<StructureSection load='2b07' size='340' side='right'caption='[[2b07]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
<StructureSection load='2b07' size='340' side='right'caption='[[2b07]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2b07]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B07 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2B07 FirstGlance]. <br>
<table><tr><td colspan='2'>[[2b07]] 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=2B07 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2B07 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=598:6-{[1-(BENZYLSULFONYL)PIPERIDIN-4-YL]AMINO}-3-(CARBOXYMETHOXY)THIENO[3,2-B][1]BENZOTHIOPHENE-2-CARBOXYLIC+ACID'>598</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]] 2.1&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2azr|2azr]]</div></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=598:6-{[1-(BENZYLSULFONYL)PIPERIDIN-4-YL]AMINO}-3-(CARBOXYMETHOXY)THIENO[3,2-B][1]BENZOTHIOPHENE-2-CARBOXYLIC+ACID'>598</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPN1, PTP1B ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=2b07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b07 OCA], [https://pdbe.org/2b07 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2b07 RCSB], [https://www.ebi.ac.uk/pdbsum/2b07 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2b07 ProSAT]</span></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=2b07 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b07 OCA], [https://pdbe.org/2b07 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2b07 RCSB], [https://www.ebi.ac.uk/pdbsum/2b07 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2b07 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[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>
[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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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2b07 ConSurf].
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2b07 ConSurf].
<div style="clear:both"></div>
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
A novel pyridothiophene inhibitor of PTP1B was discovered by rational screening of phosphotyrosine mimics at high micromolar concentrations. The potency of this lead compound has been improved significantly by medicinal chemistry guided by X-ray crystallography and molecular modeling. Excellent consistency has been observed between structure-activity relationships and structural information from PTP1B-inhibitor complexes.
Bicyclic and tricyclic thiophenes as protein tyrosine phosphatase 1B inhibitors.,Moretto AF, Kirincich SJ, Xu WX, Smith MJ, Wan ZK, Wilson DP, Follows BC, Binnun E, Joseph-McCarthy D, Foreman K, Erbe DV, Zhang YL, Tam SK, Tam SY, Lee J Bioorg Med Chem. 2006 Apr 1;14(7):2162-77. Epub 2005 Nov 21. PMID:16303309<ref>PMID:16303309</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2b07" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Protein-tyrosine-phosphatase]]
[[Category: Binnun E]]
[[Category: Binnun, E]]
[[Category: Erbe DV]]
[[Category: Erbe, D V]]
[[Category: Follows BC]]
[[Category: Follows, B C]]
[[Category: Foreman K]]
[[Category: Foreman, K]]
[[Category: Joseph-McCarthy D]]
[[Category: Joseph-McCarthy, D]]
[[Category: Kirincich SJ]]
[[Category: Kirincich, S J]]
[[Category: Lee J]]
[[Category: Lee, J]]
[[Category: Moretto AF]]
[[Category: Moretto, A F]]
[[Category: Smith MJ]]
[[Category: Smith, M J]]
[[Category: Tam SK]]
[[Category: Tam, S K]]
[[Category: Tam SY]]
[[Category: Tam, S Y]]
[[Category: Wan ZK]]
[[Category: Wan, Z K]]
[[Category: Wilson DP]]
[[Category: Wilson, D P]]
[[Category: Xu WX]]
[[Category: Xu, W X]]
[[Category: Zhang YL]]
[[Category: Zhang, Y L]]
[[Category: Hydrolase]]
[[Category: Hydrolyase]]
[[Category: Protein tyrosine phosphatase]]
[[Category: Tricyclic thiophene]]

Latest revision as of 12:15, 14 February 2024

Crystal structure of PTP1B with Tricyclic Thiophene inhibitor.Crystal structure of PTP1B with Tricyclic Thiophene inhibitor.

Structural highlights

2b07 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.1Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

See Also

References

  1. ↑ 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
  2. ↑ 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

2b07, resolution 2.10Å

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