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| | <StructureSection load='2fjm' size='340' side='right'caption='[[2fjm]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='2fjm' size='340' side='right'caption='[[2fjm]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2fjm]] is a 2 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=2FJM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FJM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2fjm]] is a 2 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=2FJM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FJM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=073:(4-{(2S,4E)-2-(1H-1,2,3-BENZOTRIAZOL-1-YL)-2-[4-(METHOXYCARBONYL)PHENYL]-5-PHENYLPENT-4-ENYL}PHENYL)(DIFLUORO)METHYLPHOSPHONIC+ACID'>073</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 2.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2fjn|2fjn]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=073:(4-{(2S,4E)-2-(1H-1,2,3-BENZOTRIAZOL-1-YL)-2-[4-(METHOXYCARBONYL)PHENYL]-5-PHENYLPENT-4-ENYL}PHENYL)(DIFLUORO)METHYLPHOSPHONIC+ACID'>073</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTPN1, 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=2fjm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fjm OCA], [https://pdbe.org/2fjm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fjm RCSB], [https://www.ebi.ac.uk/pdbsum/2fjm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fjm 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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2fjm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fjm OCA], [http://pdbe.org/2fjm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2fjm RCSB], [http://www.ebi.ac.uk/pdbsum/2fjm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2fjm 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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| | ==See Also== | | ==See Also== |
| - | *[[Tyrosine phosphatase|Tyrosine phosphatase]] | + | *[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Protein-tyrosine-phosphatase]]
| + | [[Category: Asante-Appiah E]] |
| - | [[Category: Asante-Appiah, E]] | + | [[Category: Becker JW]] |
| - | [[Category: Becker, J W]] | + | [[Category: Desponts C]] |
| - | [[Category: Desponts, C]] | + | [[Category: Dufresne C]] |
| - | [[Category: Dufresne, C]] | + | [[Category: Friesen R]] |
| - | [[Category: Friesen, R]] | + | [[Category: Lau C]] |
| - | [[Category: Lau, C]] | + | [[Category: Leblanc Y]] |
| - | [[Category: Leblanc, Y]] | + | [[Category: Patel S]] |
| - | [[Category: Patel, S]] | + | [[Category: Scapin G]] |
| - | [[Category: Scapin, G]] | + | [[Category: Taylor JM]] |
| - | [[Category: Taylor, J M]] | + | [[Category: Therien M]] |
| - | [[Category: Therien, M]] | + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Phosphatase]]
| + | |
| - | [[Category: Secondary binding site]]
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| - | [[Category: Selectivity]]
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| 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
PTP-1B represents an attractive target for the treatment of type 2 diabetes and obesity. Given the role that protein phosphatases play in the regulation of many biologically relevant processes, inhibitors against PTP-1B must be not only potent, but also selective. It has been extremely difficult to synthesize inhibitors that are selective over the highly homologous TCPTP. We have successfully exploited the conservative Leu119 to Val substitution between the two enzymes to synthesize a PTP-1B inhibitor that is an order of magnitude more selective over TCPTP. Structural analyses of PTP-1B/inhibitor complexes show a conformation-assisted inhibition mechanism as the basis for selectivity. Such an inhibitory mechanism may be applicable to other homologous enzymes.
Conformation-assisted inhibition of protein-tyrosine phosphatase-1B elicits inhibitor selectivity over T-cell protein-tyrosine phosphatase.,Asante-Appiah E, Patel S, Desponts C, Taylor JM, Lau C, Dufresne C, Therien M, Friesen R, Becker JW, Leblanc Y, Kennedy BP, Scapin G J Biol Chem. 2006 Mar 24;281(12):8010-5. Epub 2006 Jan 6. PMID:16407290[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
- ↑ Asante-Appiah E, Patel S, Desponts C, Taylor JM, Lau C, Dufresne C, Therien M, Friesen R, Becker JW, Leblanc Y, Kennedy BP, Scapin G. Conformation-assisted inhibition of protein-tyrosine phosphatase-1B elicits inhibitor selectivity over T-cell protein-tyrosine phosphatase. J Biol Chem. 2006 Mar 24;281(12):8010-5. Epub 2006 Jan 6. PMID:16407290 doi:10.1074/jbc.M511827200
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