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New page: left|200px<br /> <applet load="1xbo" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xbo, resolution 2.50Å" /> '''PTP1B complexed wit...
 
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[[Image:1xbo.gif|left|200px]]<br />
<applet load="1xbo" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1xbo, resolution 2.50&Aring;" />
'''PTP1B complexed with Isoxazole Carboxylic Acid'''<br />


==Overview==
==PTP1B complexed with Isoxazole Carboxylic Acid==
Guided by X-ray crystallography, we have extended the structure-activity, relationship (SAR) study on an isoxazole carboxylic acid-based PTP1B, inhibitor (1) and more potent and equally selective (&gt;20-fold selectivity, over the highly homologous T-cell PTPase, TCPTP) PTP1B inhibitors were, identified. Inhibitor 7 demonstrated good cellular activity against PTP1B, in COS 7 cells.
<StructureSection load='1xbo' size='340' side='right'caption='[[1xbo]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1xbo]] 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=1XBO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XBO 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]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IX1:5-(3-{3-[3-HYDROXY-2-(METHOXYCARBONYL)PHENOXY]PROPENYL}PHENYL)-4-(HYDROXYMETHYL)ISOXAZOLE-3-CARBOXYLIC+ACID'>IX1</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=1xbo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xbo OCA], [https://pdbe.org/1xbo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xbo RCSB], [https://www.ebi.ac.uk/pdbsum/1xbo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xbo 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/xb/1xbo_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=1xbo ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Guided by X-ray crystallography, we have extended the structure-activity relationship (SAR) study on an isoxazole carboxylic acid-based PTP1B inhibitor (1) and more potent and equally selective (&gt;20-fold selectivity over the highly homologous T-cell PTPase, TCPTP) PTP1B inhibitors were identified. Inhibitor 7 demonstrated good cellular activity against PTP1B in COS 7 cells.


==Disease==
Isoxazole carboxylic acids as protein tyrosine phosphatase 1B (PTP1B) inhibitors.,Zhao H, Liu G, Xin Z, Serby MD, Pei Z, Szczepankiewicz BG, Hajduk PJ, Abad-Zapatero C, Hutchins CW, Lubben TH, Ballaron SJ, Haasch DL, Kaszubska W, Rondinone CM, Trevillyan JM, Jirousek MR Bioorg Med Chem Lett. 2004 Nov 15;14(22):5543-6. PMID:15482920<ref>PMID:15482920</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>
1XBO 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 IX1 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=1XBO OCA].
</div>
<div class="pdbe-citations 1xbo" style="background-color:#fffaf0;"></div>


==Reference==
==See Also==
Isoxazole carboxylic acids as protein tyrosine phosphatase 1B (PTP1B) inhibitors., Zhao H, Liu G, Xin Z, Serby MD, Pei Z, Szczepankiewicz BG, Hajduk PJ, Abad-Zapatero C, Hutchins CW, Lubben TH, Ballaron SJ, Haasch DL, Kaszubska W, Rondinone CM, Trevillyan JM, Jirousek MR, Bioorg Med Chem Lett. 2004 Nov 15;14(22):5543-6. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15482920 15482920]
*[[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 PJ]]
[[Category: Hajduk, P.J.]]
[[Category: Hassach DL]]
[[Category: Hassach, D.L.]]
[[Category: Hutchins CW]]
[[Category: Hutchins, C.W.]]
[[Category: Jirousek MR]]
[[Category: Jirousek, M.R.]]
[[Category: Kaszubska W]]
[[Category: Kaszubska, W.]]
[[Category: Liu G]]
[[Category: Liu, G.]]
[[Category: Lubben TH]]
[[Category: Lubben, T.H.]]
[[Category: Pei Z]]
[[Category: Pei, Z.]]
[[Category: Rondinone CM]]
[[Category: Rondinone, C.M.]]
[[Category: Serby M]]
[[Category: Serby, M.]]
[[Category: Szczepankiewicz BG]]
[[Category: Szczepankiewicz, B.G.]]
[[Category: Trevillyan JM]]
[[Category: Trevillyan, J.M.]]
[[Category: Xin Z]]
[[Category: Xin, Z.]]
[[Category: Zhao H]]
[[Category: Zhao, H.]]
[[Category: IX1]]
[[Category: isoxazole carboxylic acid]]
[[Category: protein tyrosine phosphatase 1b]]
[[Category: ptp1b]]
 
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