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New page: left|200px<br /> <applet load="1ph0" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ph0, resolution 2.20Å" /> '''Non-carboxylic Acid...
 
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[[Image:1ph0.gif|left|200px]]<br />
<applet load="1ph0" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1ph0, resolution 2.20&Aring;" />
'''Non-carboxylic Acid-Containing Inhibitor of PTP1B Targeting the Second Phosphotyrosine Site'''<br />


==Overview==
==Non-carboxylic Acid-Containing Inhibitor of PTP1B Targeting the Second Phosphotyrosine Site==
Protein tyrosine phosphatase (PTPase) 1B (PTP1B) has been implicated as a, key negative regulator of both insulin and leptin signaling cascades. We, identified several salicylic acid-based ligands for the second, phosphotyrosine binding site of PTP1B using a NMR-based screening., Structure-based linking with a catalytic site-directed, oxalylarylaminobenzoic acid-based pharmacophore led to the identification, of a novel series of potent PTP1B inhibitors exhibiting 6-fold selectivity, over the highly homologous T-cell PTPase (TCPTP) and high selectivity over, other phosphatases.
<StructureSection load='1ph0' size='340' side='right'caption='[[1ph0]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1ph0]] 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=1PH0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PH0 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=418:2-{4-[2-(S)-ALLYLOXYCARBONYLAMINO-3-{4-[(2-CARBOXY-PHENYL)-OXALYL-AMINO]-PHENYL}-PROPIONYLAMINO]-BUTOXY}-6-HYDROXY-BENZOIC+ACID+METHYL+ESTER'>418</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=1ph0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ph0 OCA], [https://pdbe.org/1ph0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ph0 RCSB], [https://www.ebi.ac.uk/pdbsum/1ph0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ph0 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/ph/1ph0_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=1ph0 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Protein tyrosine phosphatase (PTPase) 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling cascades. We identified several salicylic acid-based ligands for the second phosphotyrosine binding site of PTP1B using a NMR-based screening. Structure-based linking with a catalytic site-directed oxalylarylaminobenzoic acid-based pharmacophore led to the identification of a novel series of potent PTP1B inhibitors exhibiting 6-fold selectivity over the highly homologous T-cell PTPase (TCPTP) and high selectivity over other phosphatases.


==Disease==
Selective protein tyrosine phosphatase 1B inhibitors: targeting the second phosphotyrosine binding site with non-carboxylic acid-containing ligands.,Liu G, Xin Z, Liang H, Abad-Zapatero C, Hajduk PJ, Janowick DA, Szczepankiewicz BG, Pei Z, Hutchins CW, Ballaron SJ, Stashko MA, Lubben TH, Berg CE, Rondinone CM, Trevillyan JM, Jirousek MR J Med Chem. 2003 Jul 31;46(16):3437-40. PMID:12877578<ref>PMID:12877578</ref>
Known diseases associated with this structure: Abdominal body fat distribution, modifier of OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176885 176885]], Insulin resistance, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=176885 176885]]


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
1PH0 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with 418 as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1PH0 OCA].
</div>
<div class="pdbe-citations 1ph0" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Selective protein tyrosine phosphatase 1B inhibitors: targeting the second phosphotyrosine binding site with non-carboxylic acid-containing ligands., Liu G, Xin Z, Liang H, Abad-Zapatero C, Hajduk PJ, Janowick DA, Szczepankiewicz BG, Pei Z, Hutchins CW, Ballaron SJ, Stashko MA, Lubben TH, Berg CE, Rondinone CM, Trevillyan JM, Jirousek MR, J Med Chem. 2003 Jul 31;46(16):3437-40. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12877578 12877578]
*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein-tyrosine-phosphatase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Abad-Zapatero C]]
[[Category: Abad-Zapatero, C.]]
[[Category: Ballaron SJ]]
[[Category: Ballaron, S.J.]]
[[Category: Hajduk P]]
[[Category: Hajduk, P.]]
[[Category: Hutchins CW]]
[[Category: Hutchins, C.W.]]
[[Category: Janowick D]]
[[Category: Janowick, D.]]
[[Category: Liang H]]
[[Category: Liang, H.]]
[[Category: Liu G]]
[[Category: Liu, G.]]
[[Category: Pei Z]]
[[Category: Pei, Z.]]
[[Category: Szczepankiewicz B]]
[[Category: Szczepankiewicz, B.]]
[[Category: Xin Z]]
[[Category: Xin, Z.]]
[[Category: 418]]
[[Category: oxalyl-aryl-benzoic acid compound inhibitor]]
[[Category: protein tyrosine phosphatase 1b]]
[[Category: salicylic acid moiety at the second site]]
 
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