1nwl

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[[Image:1nwl.gif|left|200px]]
 
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==Crystal structure of the PTP1B complexed with SP7343-SP7964, a pTyr mimetic==
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The line below this paragraph, containing "STRUCTURE_1nwl", creates the "Structure Box" on the page.
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<StructureSection load='1nwl' size='340' side='right'caption='[[1nwl]], [[Resolution|resolution]] 2.40&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'>[[1nwl]] 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=1NWL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NWL 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]] 2.4&#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=964:3-(4-{2-[2-(2-BROMO-ACETYLAMINO)-ETHYLDISULFANYL]-ETHYLCARBAMOYL}-CYCLOHEXYLCARBAMOYL)-PYRAZINE-2-CARBOXYLIC+ACID'>964</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
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{{STRUCTURE_1nwl| PDB=1nwl | 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=1nwl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nwl OCA], [https://pdbe.org/1nwl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nwl RCSB], [https://www.ebi.ac.uk/pdbsum/1nwl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nwl 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/nw/1nwl_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=1nwl ConSurf].
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<div style="clear:both"></div>
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'''Crystal structure of the PTP1B complexed with SP7343-SP7964, a pTyr mimetic'''
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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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Protein tyrosine phosphatases play important roles in many signaling cascades involved in human disease. The identification of druglike inhibitors for these targets is a major challenge, and the discovery of suitable phosphotyrosine (pY) mimetics remains one of the key difficulties. Here we describe an extension of tethering technology, "breakaway tethering", which is ideally suited for discovering such new chemical entities. The approach involves first irreversibly modifying a protein with an extender that contains both a masked thiol and a known pY mimetic. The extender is then cleaved to release the pY mimetic, unmasking the thiol. The resulting protein is screened against a library of disulfide-containing small molecule fragments; any molecules with inherent affinity for the pY binding site will preferentially form disulfides with the extender, allowing for their identification by mass spectrometry. The ability to start from a known substrate mimimizes perturbation of protein structure and increases the opportunity to probe the active site using tethering. We applied this approach to the anti-diabetic protein PTP1B to discover a pY mimetic which belongs to a new molecular class and which binds in a novel fashion.
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__TOC__
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</StructureSection>
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==Disease==
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Known disease 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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==About this Structure==
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1NWL 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=1NWL OCA].
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==Reference==
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Discovery of a new phosphotyrosine mimetic for PTP1B using breakaway tethering., Erlanson DA, McDowell RS, He MM, Randal M, Simmons RL, Kung J, Waight A, Hansen SK, J Am Chem Soc. 2003 May 14;125(19):5602-3. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12733877 12733877]
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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: Erlanson DA]]
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[[Category: Erlanson, D A.]]
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[[Category: Hansen S]]
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[[Category: Hansen, S.]]
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[[Category: He MM]]
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[[Category: He, M M.]]
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[[Category: Kung J]]
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[[Category: Kung, J.]]
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[[Category: McDowell RS]]
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[[Category: McDowell, R S.]]
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[[Category: Randal M]]
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[[Category: Randal, M.]]
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[[Category: Simmons RL]]
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[[Category: Simmons, R L.]]
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[[Category: Waight A]]
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[[Category: Waight, A.]]
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[[Category: Protein-small molecule inhibitor complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 03:03:58 2008''
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Current revision

Crystal structure of the PTP1B complexed with SP7343-SP7964, a pTyr mimetic

PDB ID 1nwl

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