1ecv

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[[Image:1ecv.jpg|left|200px]]<br /><applet load="1ecv" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="1ecv, resolution 1.95&Aring;" />
 
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'''CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH 5-IODO-2-(OXALYL-AMINO)-BENZOIC ACID'''<br />
 
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==Overview==
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==CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH 5-IODO-2-(OXALYL-AMINO)-BENZOIC ACID==
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Protein-tyrosine phosphatases (PTPs) are critically involved in regulation, of signal transduction processes. Members of this class of enzymes are, considered attractive therapeutic targets in several disease states, e.g., diabetes, cancer, and inflammation. However, most reported PTP inhibitors, have been phosphorus-containing compounds, tight binding inhibitors, and/or inhibitors that covalently modify the enzymes. We therefore, embarked on identifying a general, reversible, competitive PTP inhibitor, that could be used as a common scaffold for lead optimization for specific, PTPs. We here report the identification of 2-(oxalylamino)-benzoic acid, (OBA) as a classical competitive inhibitor of several PTPs. X-ray, crystallography of PTP1B complexed with OBA and related non-phosphate low, molecular weight derivatives reveals that the binding mode of these, molecules to a large extent mimics that of the natural substrate including, hydrogen bonding to the PTP signature motif. In addition, binding of OBA, to the active site of PTP1B creates a unique arrangement involving, Asp(181), Lys(120), and Tyr(46). PTP inhibitors are essential tools in, elucidating the biological function of specific PTPs and they may, eventually be developed into selective drug candidates. The unique enzyme, kinetic features and the low molecular weight of OBA makes it an ideal, starting point for further optimization.
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<StructureSection load='1ecv' size='340' side='right'caption='[[1ecv]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1ecv]] 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=1ECV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ECV FirstGlance]. <br>
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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]] 1.95&#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=878:5-IODO-2-(OXALYL-AMINO)-BENZOIC+ACID'>878</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene></td></tr>
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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=1ecv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ecv OCA], [https://pdbe.org/1ecv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ecv RCSB], [https://www.ebi.ac.uk/pdbsum/1ecv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ecv 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/ec/1ecv_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=1ecv ConSurf].
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<div style="clear:both"></div>
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==Disease==
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==See Also==
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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]]
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*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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1ECV 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 <scene name='pdbligand=ACT:'>ACT</scene> and <scene name='pdbligand=878:'>878</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. 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://oca.weizmann.ac.il/oca-bin/ocashort?id=1ECV OCA].
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__TOC__
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</StructureSection>
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==Reference==
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2-(oxalylamino)-benzoic acid is a general, competitive inhibitor of protein-tyrosine phosphatases., Andersen HS, Iversen LF, Jeppesen CB, Branner S, Norris K, Rasmussen HB, Moller KB, Moller NP, J Biol Chem. 2000 Mar 10;275(10):7101-8. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10702277 10702277]
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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: Andersen HS]]
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[[Category: Andersen, H.S.]]
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[[Category: Branner S]]
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[[Category: Branner, S.]]
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[[Category: Iversen LF]]
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[[Category: Iversen, L.F.]]
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[[Category: Moller NPH]]
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[[Category: Moller, N.P.H.]]
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[[Category: Rasmussen HB]]
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[[Category: Rasmussen, H.B.]]
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[[Category: 878]]
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[[Category: ACT]]
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[[Category: hydrolase]]
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[[Category: inhibitor]]
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[[Category: ligand]]
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[[Category: phosphorylation]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 15:42:27 2008''
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Current revision

CRYSTAL STRUCTURE OF PROTEIN TYROSINE PHOSPHATASE 1B COMPLEXED WITH 5-IODO-2-(OXALYL-AMINO)-BENZOIC ACID

PDB ID 1ecv

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