1pxh

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{{Seed}}
 
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[[Image:1pxh.png|left|200px]]
 
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==Crystal structure of protein tyrosine phosphatase 1B with potent and selective bidentate inhibitor compound 2==
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The line below this paragraph, containing "STRUCTURE_1pxh", creates the "Structure Box" on the page.
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<StructureSection load='1pxh' size='340' side='right'caption='[[1pxh]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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== Structural highlights ==
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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<table><tr><td colspan='2'>[[1pxh]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1n6w 1n6w]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PXH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PXH FirstGlance]. <br>
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or leave the SCENE parameter empty for the default display.
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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]] 2.15&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACY:ACETIC+ACID'>ACY</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SNA:N-{1-[5-(1-CARBAMOYL-2-MERCAPTO-ETHYLCARBAMOYL)-PENTYLCARBAMOYL]-2-[4-(DIFLUORO-PHOSPHONO-METHYL)-PHENYL]-ETHYL}-3-{2-[4-(DIFLUORO-PHOSPHONO-METHYL)-PHENYL]-ACETYLAMINO}-SUCCINAMIC+ACID'>SNA</scene></td></tr>
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{{STRUCTURE_1pxh| PDB=1pxh | SCENE= }}
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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=1pxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pxh OCA], [https://pdbe.org/1pxh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pxh RCSB], [https://www.ebi.ac.uk/pdbsum/1pxh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pxh ProSAT]</span></td></tr>
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</table>
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== Function ==
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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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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/px/1pxh_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=1pxh 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 ==
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Protein-tyrosine phosphatase 1B (PTP1B) has been implicated as an important regulator in several signaling pathways including those initiated by insulin and leptin. Potent and specific PTP1B inhibitors could serve as useful tools in elucidating the physiological functions of PTP1B and may constitute valuable therapeutics in the treatment of several human diseases. We have determined the crystal structure of PTP1B in complex with compound 2, the most potent and selective PTP1B inhibitor reported to date. The structure at 2.15-A resolution reveals that compound 2 simultaneously binds to the active site and a unique proximal noncatalytic site formed by Lys-41, Arg-47, and Asp-48. The structural data are further corroborated by results from kinetic analyses of the interactions of PTP1B and its site-directed mutants with compound 2 and several of its variants. Although many of the residues important for interactions between PTP1B and compound 2 are not unique to PTP1B, the combinations of all contact residues differ between PTP isozymes, which provide a structural basis for potent and selective PTP1B inhibition. Our data further suggest that potent, yet highly selective, PTP1B inhibitory agents can be acquired by targeting the area defined by residues Lys-41, Arg-47, and Asp-48, in addition to the previously identified second aryl phosphate-binding pocket.
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===Crystal structure of protein tyrosine phosphatase 1B with potent and selective bidentate inhibitor compound 2===
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Crystal structure of PTP1B complexed with a potent and selective bidentate inhibitor.,Sun JP, Fedorov AA, Lee SY, Guo XL, Shen K, Lawrence DS, Almo SC, Zhang ZY J Biol Chem. 2003 Apr 4;278(14):12406-14. Epub 2003 Jan 23. PMID:12547827<ref>PMID:12547827</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 1pxh" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_12547827}}, adds the Publication Abstract to the page
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*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 12547827 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_12547827}}
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__TOC__
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</StructureSection>
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==About this Structure==
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1PXH is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1n6w 1n6w]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PXH OCA].
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==Reference==
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Crystal structure of PTP1B complexed with a potent and selective bidentate inhibitor., Sun JP, Fedorov AA, Lee SY, Guo XL, Shen K, Lawrence DS, Almo SC, Zhang ZY, J Biol Chem. 2003 Apr 4;278(14):12406-14. Epub 2003 Jan 23. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12547827 12547827]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein-tyrosine-phosphatase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Almo SC]]
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[[Category: Almo, S C.]]
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[[Category: Fedorov A]]
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[[Category: Fedorov, A.]]
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[[Category: Guo XL]]
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[[Category: Guo, X L.]]
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[[Category: Lawrence DS]]
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[[Category: Lawrence, D S.]]
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[[Category: Lee SY]]
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[[Category: Lee, S Y.]]
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[[Category: Shen K]]
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[[Category: Shen, K.]]
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[[Category: Sun JP]]
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[[Category: Sun, J P.]]
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[[Category: Zhang ZY]]
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[[Category: Zhang, Z Y.]]
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[[Category: Phosphatase inhibitor]]
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[[Category: Protein tyrosine phosphatase]]
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[[Category: Ptp1b]]
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[[Category: X-ray diffraction]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 00:08:02 2008''
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Current revision

Crystal structure of protein tyrosine phosphatase 1B with potent and selective bidentate inhibitor compound 2

PDB ID 1pxh

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