1no6

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[[Image:1no6.jpg|left|200px]]
 
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==Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Compound 5 Using a Linked-Fragment Strategy==
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The line below this paragraph, containing "STRUCTURE_1no6", creates the "Structure Box" on the page.
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<StructureSection load='1no6' size='340' side='right'caption='[[1no6]], [[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'>[[1no6]] 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=1NO6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NO6 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=794:2-[(CARBOXYCARBONYL)(1-NAPHTHYL)AMINO]BENZOIC+ACID'>794</scene></td></tr>
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{{STRUCTURE_1no6| PDB=1no6 | 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=1no6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1no6 OCA], [https://pdbe.org/1no6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1no6 RCSB], [https://www.ebi.ac.uk/pdbsum/1no6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1no6 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/no/1no6_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=1no6 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Protein tyrosine phosphatase 1B (PTP1B) is an enzyme that downregulates the insulin receptor. Inhibition of PTP1B is expected to improve insulin action, and the design of small molecule PTP1B inhibitors to treat type II diabetes has received considerable attention. In this work, NMR-based screening identified a nonselective competitive inhibitor of PTP1B. A second site ligand was also identified by NMR-based screening and then linked to the catalytic site ligand by rational design. X-ray data confirmed that the inhibitor bound with the catalytic site in the native, "open" conformation. The final compound displayed excellent potency and good selectivity over many other phosphatases. The modular approach to drug design described in this work should be applicable for the design of potent and selective inhibitors of other therapeutically relevant protein tyrosine phosphatases.
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'''Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Compound 5 Using a Linked-Fragment Strategy'''
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Discovery of a potent, selective protein tyrosine phosphatase 1B inhibitor using a linked-fragment strategy.,Szczepankiewicz BG, Liu G, Hajduk PJ, Abad-Zapatero C, Pei Z, Xin Z, Lubben TH, Trevillyan JM, Stashko MA, Ballaron SJ, Liang H, Huang F, Hutchins CW, Fesik SW, Jirousek MR J Am Chem Soc. 2003 Apr 9;125(14):4087-96. PMID:12670229<ref>PMID:12670229</ref>
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==Overview==
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Protein tyrosine phosphatase 1B (PTP1B) is an enzyme that downregulates the insulin receptor. Inhibition of PTP1B is expected to improve insulin action, and the design of small molecule PTP1B inhibitors to treat type II diabetes has received considerable attention. In this work, NMR-based screening identified a nonselective competitive inhibitor of PTP1B. A second site ligand was also identified by NMR-based screening and then linked to the catalytic site ligand by rational design. X-ray data confirmed that the inhibitor bound with the catalytic site in the native, "open" conformation. The final compound displayed excellent potency and good selectivity over many other phosphatases. The modular approach to drug design described in this work should be applicable for the design of potent and selective inhibitors of other therapeutically relevant protein tyrosine phosphatases.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1NO6 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=1NO6 OCA].
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</div>
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<div class="pdbe-citations 1no6" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Discovery of a potent, selective protein tyrosine phosphatase 1B inhibitor using a linked-fragment strategy., Szczepankiewicz BG, Liu G, Hajduk PJ, Abad-Zapatero C, Pei Z, Xin Z, Lubben TH, Trevillyan JM, Stashko MA, Ballaron SJ, Liang H, Huang F, Hutchins CW, Fesik SW, Jirousek MR, J Am Chem Soc. 2003 Apr 9;125(14):4087-96. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12670229 12670229]
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*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[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: Abad-Zapatero C]]
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[[Category: Abad-Zapatero, C.]]
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[[Category: Ballaron SJ]]
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[[Category: Ballaron, S J.]]
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[[Category: Fesik SW]]
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[[Category: Fesik, S W.]]
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[[Category: Hajduk PJ]]
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[[Category: Hajduk, P J.]]
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[[Category: Huang F]]
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[[Category: Huang, F.]]
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[[Category: Hutchins CW]]
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[[Category: Hutchins, C W.]]
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[[Category: Jirousek MR]]
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[[Category: Jirousek, M R.]]
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[[Category: Liang H]]
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[[Category: Liang, H.]]
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[[Category: Liu G]]
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[[Category: Liu, G.]]
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[[Category: Lubben T]]
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[[Category: Lubben, T.]]
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[[Category: Pei Z]]
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[[Category: Pei, Z.]]
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[[Category: Stashko MA]]
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[[Category: Stashko, M A.]]
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[[Category: Szczepankiewicz BG]]
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[[Category: Szczepankiewicz, B G.]]
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[[Category: Trevillyan JM]]
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[[Category: Trevillyan, J M.]]
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[[Category: Xin Z]]
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[[Category: Xin, Z.]]
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[[Category: Oxamic acid inhibitor bound to p-loop]]
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[[Category: Protein tyrosine phosphatase fold]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 02:46:17 2008''
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Current revision

Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Compound 5 Using a Linked-Fragment Strategy

PDB ID 1no6

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