2b4s

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[[Image:2b4s.gif|left|200px]]
 
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{{Structure
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==Crystal structure of a complex between PTP1B and the insulin receptor tyrosine kinase==
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|PDB= 2b4s |SIZE=350|CAPTION= <scene name='initialview01'>2b4s</scene>, resolution 2.30&Aring;
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<StructureSection load='2b4s' size='340' side='right'caption='[[2b4s]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND= <scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>
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<table><tr><td colspan='2'>[[2b4s]] is a 4 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=2B4S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2B4S FirstGlance]. <br>
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|ACTIVITY= <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>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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|GENE= PTPN1, PTP1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), INSR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PTR:O-PHOSPHOTYROSINE'>PTR</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
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|DOMAIN=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2b4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b4s OCA], [https://pdbe.org/2b4s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2b4s RCSB], [https://www.ebi.ac.uk/pdbsum/2b4s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2b4s ProSAT]</span></td></tr>
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|RELATEDENTRY=
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</table>
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2b4s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2b4s OCA], [http://www.ebi.ac.uk/pdbsum/2b4s PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2b4s RCSB]</span>
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== Function ==
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}}
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[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>
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== Evolutionary Conservation ==
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'''Crystal structure of a complex between PTP1B and the insulin receptor tyrosine kinase'''
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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==Overview==
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b4/2b4s_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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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=2b4s ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
Protein tyrosine phosphatase 1B (PTP1B) is a highly specific negative regulator of insulin receptor signaling in vivo. The determinants of PTP1B specificity for the insulin receptor versus other receptor tyrosine kinases are largely unknown. Here, we report a crystal structure at 2.3 A resolution of the catalytic domain of PTP1B (trapping mutant) in complex with the phosphorylated tyrosine kinase domain of the insulin receptor (IRK). The crystallographic asymmetric unit contains two PTP1B-IRK complexes that interact through an IRK dimer interface. Rather than binding to a phosphotyrosine in the IRK activation loop, PTP1B binds instead to the opposite side of the kinase domain, with the phosphorylated activation loops sequestered within the IRK dimer. The crystal structure provides evidence for a noncatalytic mode of interaction between PTP1B and IRK, which could be important for the selective recruitment of PTP1B to the insulin receptor.
Protein tyrosine phosphatase 1B (PTP1B) is a highly specific negative regulator of insulin receptor signaling in vivo. The determinants of PTP1B specificity for the insulin receptor versus other receptor tyrosine kinases are largely unknown. Here, we report a crystal structure at 2.3 A resolution of the catalytic domain of PTP1B (trapping mutant) in complex with the phosphorylated tyrosine kinase domain of the insulin receptor (IRK). The crystallographic asymmetric unit contains two PTP1B-IRK complexes that interact through an IRK dimer interface. Rather than binding to a phosphotyrosine in the IRK activation loop, PTP1B binds instead to the opposite side of the kinase domain, with the phosphorylated activation loops sequestered within the IRK dimer. The crystal structure provides evidence for a noncatalytic mode of interaction between PTP1B and IRK, which could be important for the selective recruitment of PTP1B to the insulin receptor.
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==Disease==
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Crystal structure of a complex between protein tyrosine phosphatase 1B and the insulin receptor tyrosine kinase.,Li S, Depetris RS, Barford D, Chernoff J, Hubbard SR Structure. 2005 Nov;13(11):1643-51. PMID:16271887<ref>PMID:16271887</ref>
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Known disease associated with this structure: Diabetes mellitus, insulin-resistant, with acanthosis nigricans OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]], Hyperinsulinemic hypoglycemia, familial, 5 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]], Leprechaunism OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]], Rabson-Mendenhall syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147670 147670]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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2B4S is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2B4S OCA].
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</div>
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<div class="pdbe-citations 2b4s" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Crystal structure of a complex between protein tyrosine phosphatase 1B and the insulin receptor tyrosine kinase., Li S, Depetris RS, Barford D, Chernoff J, Hubbard SR, Structure. 2005 Nov;13(11):1643-51. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16271887 16271887]
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*[[Insulin receptor 3D structures|Insulin receptor 3D structures]]
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*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Protein-tyrosine-phosphatase]]
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[[Category: Barford D]]
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[[Category: Barford, D.]]
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[[Category: Chernoff J]]
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[[Category: Chernoff, J.]]
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[[Category: Depetris RS]]
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[[Category: Depetris, R S.]]
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[[Category: Hubbard SR]]
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[[Category: Hubbard, S R.]]
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[[Category: Li S]]
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[[Category: Li, S.]]
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[[Category: hydrolase/transferase]]
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[[Category: phosphorylation]]
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[[Category: tyrosine protein kinase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 02:01:27 2008''
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Current revision

Crystal structure of a complex between PTP1B and the insulin receptor tyrosine kinase

PDB ID 2b4s

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