1l8g

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[[Image:1l8g.jpg|left|200px]]
 
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==Crystal structure of PTP1B complexed with 7-(1,1-Dioxo-1H-benzo[d]isothiazol-3-yloxymethyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid==
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The line below this paragraph, containing "STRUCTURE_1l8g", creates the "Structure Box" on the page.
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<StructureSection load='1l8g' size='340' side='right'caption='[[1l8g]], [[Resolution|resolution]] 2.50&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'>[[1l8g]] 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=1L8G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1L8G 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]] 2.5&#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=DBD:7-(1,1-DIOXO-1H-BENZO[D]ISOTHIAZOL-3-YLOXYMETHYL)-2-(OXALYL-AMINO)-4,7-DIHYDRO-5H-THIENO[2,3-C]PYRAN-3-CARBOXYLIC+ACID'>DBD</scene></td></tr>
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{{STRUCTURE_1l8g| PDB=1l8g | 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=1l8g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1l8g OCA], [https://pdbe.org/1l8g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1l8g RCSB], [https://www.ebi.ac.uk/pdbsum/1l8g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1l8g 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/l8/1l8g_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=1l8g ConSurf].
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<div style="clear:both"></div>
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'''Crystal structure of PTP1B complexed with 7-(1,1-Dioxo-1H-benzo[d]isothiazol-3-yloxymethyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid'''
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==See Also==
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*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
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== References ==
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==Overview==
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<references/>
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Utilizing structure-based design, we have previously demonstrated that it is possible to obtain selective inhibitors of protein-tyrosine phosphatase 1B (PTP1B). A basic nitrogen was introduced into a general PTP inhibitor to form a salt bridge to Asp48 in PTP1B and simultaneously cause repulsion in PTPs containing an asparagine in the equivalent position [Iversen, L. F., et al. (2000) J. Biol. Chem. 275, 10300-10307]. Further, we have recently demonstrated that Gly259 in PTP1B forms the bottom of a gateway that allows easy access to the active site for a broad range of substrates, while bulky residues in the same position in other PTPs cause steric hindrance and reduced substrate recognition capacity [Peters, G. H., et al. (2000) J. Biol. Chem. 275, 18201-18209]. The current study was undertaken to investigate the feasibility of structure-based design, utilizing these differences in accessibility to the active site among various PTPs. We show that a general, low-molecular weight PTP inhibitor can be developed into a highly selective inhibitor for PTP1B and TC-PTP by introducing a substituent, which is designed to address the region around residues 258 and 259. Detailed enzyme kinetic analysis with a set of wild-type and mutant PTPs, X-ray protein crystallography, and molecular modeling studies confirmed that selectivity for PTP1B and TC-PTP was achieved due to steric hindrance imposed by bulky position 259 residues in other PTPs.
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__TOC__
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</StructureSection>
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==About this Structure==
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1L8G is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L8G OCA].
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==Reference==
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Steric hindrance as a basis for structure-based design of selective inhibitors of protein-tyrosine phosphatases., Iversen LF, Andersen HS, Moller KB, Olsen OH, Peters GH, Branner S, Mortensen SB, Hansen TK, Lau J, Ge Y, Holsworth DD, Newman MJ, Hundahl Moller NP, Biochemistry. 2001 Dec 11;40(49):14812-20. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11732900 11732900]
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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: Ge Y]]
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[[Category: Ge, Y.]]
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[[Category: Hansen TK]]
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[[Category: Hansen, T K.]]
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[[Category: Holsworth DD]]
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[[Category: Holsworth, D D.]]
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[[Category: Iversen LF]]
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[[Category: Iversen, L F.]]
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[[Category: Lau J]]
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[[Category: Lau, J.]]
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[[Category: Moller KB]]
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[[Category: Moller, K B.]]
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[[Category: Moller NPH]]
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[[Category: Moller, N P.H.]]
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[[Category: Mortensen SB]]
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[[Category: Mortensen, S B.]]
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[[Category: Newman MJ]]
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[[Category: Newman, M J.]]
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[[Category: Olsen OH]]
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[[Category: Olsen, O H.]]
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[[Category: Peters GH]]
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[[Category: Peters, G H.]]
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[[Category: Protein-inhibitor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 23:39:44 2008''
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Current revision

Crystal structure of PTP1B complexed with 7-(1,1-Dioxo-1H-benzo[d]isothiazol-3-yloxymethyl)-2-(oxalyl-amino)-4,7-dihydro-5H-thieno[2,3-c]pyran-3-carboxylic acid

PDB ID 1l8g

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