1nny

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[[Image:1nny.png|left|200px]]
 
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{{STRUCTURE_1nny| PDB=1nny | SCENE= }}
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==Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Compound 23 Using a Linked-Fragment Strategy==
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<StructureSection load='1nny' size='340' side='right'caption='[[1nny]], [[Resolution|resolution]] 2.40&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1nny]] 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=1NNY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NNY 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]] 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=515:3-({5-[(N-ACETYL-3-{4-[(CARBOXYCARBONYL)(2-CARBOXYPHENYL)AMINO]-1-NAPHTHYL}-L-ALANYL)AMINO]PENTYL}OXY)-2-NAPHTHOIC+ACID'>515</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=1nny FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1nny OCA], [https://pdbe.org/1nny PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1nny RCSB], [https://www.ebi.ac.uk/pdbsum/1nny PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1nny 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/nn/1nny_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=1nny 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 23 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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{{ABSTRACT_PUBMED_12670229}}
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==About this Structure==
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<div class="pdbe-citations 1nny" style="background-color:#fffaf0;"></div>
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[[1nny]] is a 1 chain structure of [[Tyrosine phosphatase]] with 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=1NNY OCA].
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==See Also==
==See Also==
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*[[Tyrosine phosphatase|Tyrosine phosphatase]]
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*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:012670229</ref><ref group="xtra">PMID:015258570</ref><references group="xtra"/>
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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: Abad-Zapatero, C.]]
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[[Category: Abad-Zapatero C]]
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[[Category: Ballaron, S J.]]
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[[Category: Ballaron SJ]]
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[[Category: Fesik, S W.]]
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[[Category: Fesik SW]]
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[[Category: Hajduk, P J.]]
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[[Category: Hajduk PJ]]
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[[Category: Huang, F.]]
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[[Category: Huang F]]
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[[Category: Hutchins, C W.]]
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[[Category: Hutchins CW]]
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[[Category: Jirousek, M R.]]
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[[Category: Jirousek MR]]
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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, M A.]]
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[[Category: Stashko MA]]
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[[Category: Szczepankiewicz, B G.]]
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[[Category: Szczepankiewicz BG]]
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[[Category: Trevillyan, J M.]]
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[[Category: Trevillyan JM]]
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[[Category: Xin, Z.]]
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[[Category: Xin Z]]
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[[Category: Dual-site oxamic acid inhibitor bound to p-loop]]
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[[Category: Hydrolase]]
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[[Category: Protein tyrosine phosphatase fold]]
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Current revision

Potent, Selective Protein Tyrosine Phosphatase 1B Inhibitor Compound 23 Using a Linked-Fragment Strategy

PDB ID 1nny

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