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==POTENT, SELECTIVE INHIBITORS OF PROTEIN TYROSINE PHOSPHATASE 1B USING A SECOND PHOSPHOTYROSINE BINDING SITE, complexed with compound 19.== | |||
<StructureSection load='1nz7' size='340' side='right'caption='[[1nz7]], [[Resolution|resolution]] 2.40Å' scene=''> | |||
| | == Structural highlights == | ||
<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='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='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='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> | |||
</table> | |||
== 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> | |||
== Evolutionary Conservation == | |||
== | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nz/1nz7_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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=1nz7 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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. | 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<ref>PMID:12749891</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 1nz7" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: Abad-Zapatero C]] | |||
[[Category: Abad-Zapatero | [[Category: Ballaron SJ]] | ||
[[Category: Ballaron | [[Category: Hajduk PJ]] | ||
[[Category: Hajduk | [[Category: Hutchins CW]] | ||
[[Category: Hutchins | [[Category: Jirousek MR]] | ||
[[Category: Jirousek | [[Category: Liu G]] | ||
[[Category: Liu | [[Category: Lubben T]] | ||
[[Category: Lubben | [[Category: Oost TK]] | ||
[[Category: Oost | [[Category: Pei Z]] | ||
[[Category: Pei | [[Category: Stashko MA]] | ||
[[Category: Stashko | [[Category: Szczepankiewicz BG]] | ||
[[Category: Szczepankiewicz | [[Category: Trevillyan JM]] | ||
[[Category: Trevillyan | [[Category: Xin Z]] | ||
[[Category: Xin | |||
Latest revision as of 12:27, 16 August 2023
POTENT, SELECTIVE INHIBITORS OF PROTEIN TYROSINE PHOSPHATASE 1B USING A SECOND PHOSPHOTYROSINE BINDING SITE, complexed with compound 19.POTENT, SELECTIVE INHIBITORS OF PROTEIN TYROSINE PHOSPHATASE 1B USING A SECOND PHOSPHOTYROSINE BINDING SITE, complexed with compound 19.
Structural highlights
FunctionPTN1_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 PubMedWe 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 AlsoReferences
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