1q6t: Difference between revisions

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-{{Seed}}
-[[Image:1q6t.png|left|200px]]
-<!--
+==THE STRUCTURE OF PHOSPHOTYROSINE PHOSPHATASE 1B IN COMPLEX WITH COMPOUND 11==
-The line below this paragraph, containing "STRUCTURE_1q6t", creates the "Structure Box" on the page.
+<StructureSection load='1q6t' size='340' side='right'caption='[[1q6t]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[1q6t]] is a 2 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=1Q6T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q6T FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=600:6-[4-((2S)-2-(1H-1,2,3-BENZOTRIAZOL-1-YL)-3-{4-[DIFLUORO(PHOSPHONO)METHYL]PHENYL}-2-PHENYLPROPYL)PHENYL]-2-[(1S)-1-METHOXY-3-METHYLBUTYL]QUINOLIN-8-YLPHOSPHONIC+ACID'>600</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-{{STRUCTURE_1q6t|  PDB=1q6t  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1q6t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q6t OCA], [https://pdbe.org/1q6t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q6t RCSB], [https://www.ebi.ac.uk/pdbsum/1q6t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q6t ProSAT]</span></td></tr>
+</table>
+== Function ==
+[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>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q6/1q6t_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=1q6t ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Protein tyrosine phosphatase 1B (PTP1B) has been implicated in the regulation of the insulin signaling pathway and represents an attractive target for the design of inhibitors in the treatment of type 2 diabetes and obesity. Inspection of the structure of PTP1B indicates that potent PTP1B inhibitors may be obtained by targeting a secondary aryl phosphate-binding site as well as the catalytic site. We report here the crystal structures of PTP1B in complex with first and second generation aryldifluoromethyl-phosphonic acid inhibitors. While all compounds bind in a previously unexploited binding pocket near the primary binding site, the second generation compounds also reach into the secondary binding site, and exhibit moderate selectivity for PTP1B over the closely related T-cell phosphatase. The molecular basis for the selectivity has been confirmed by single point mutation at position 52, where the two phosphatases differ by a phenylalanine-to-tyrosine switch. These compounds present a novel platform for the development of potent and selective PTP1B inhibitors.
-===THE STRUCTURE OF PHOSPHOTYROSINE PHOSPHATASE 1B IN COMPLEX WITH COMPOUND 11===
+The structural basis for the selectivity of benzotriazole inhibitors of PTP1B.,Scapin G, Patel SB, Becker JW, Wang Q, Desponts C, Waddleton D, Skorey K, Cromlish W, Bayly C, Therien M, Gauthier JY, Li CS, Lau CK, Ramachandran C, Kennedy BP, Asante-Appiah E Biochemistry. 2003 Oct 7;42(39):11451-9. PMID:14516196<ref>PMID:14516196</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 1q6t" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_14516196}}, adds the Publication Abstract to the page
+*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 14516196 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_14516196}}
+__TOC__
+</StructureSection>
-==About this Structure==
-Q6T is a 2 chains structure of sequences 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=1Q6T OCA].
-==Reference==
-<ref group="xtra">PMID:14516196</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Protein-tyrosine-phosphatase]]
+[[Category: Large Structures]]
-[[Category: Asante-Appiah, E.]]
+[[Category: Asante-Appiah E]]
-[[Category: Bayly, C.]]
+[[Category: Bayly C]]
-[[Category: Becker, J W.]]
+[[Category: Becker JW]]
-[[Category: Cromlish, W.]]
+[[Category: Cromlish W]]
-[[Category: Desponts, C.]]
+[[Category: Desponts C]]
-[[Category: Gauthier, J Y.]]
+[[Category: Gauthier JY]]
-[[Category: Kennedy, B P.]]
+[[Category: Kennedy BP]]
-[[Category: Lau, C K.]]
+[[Category: Lau CK]]
-[[Category: Li, C S.]]
+[[Category: Li CS]]
-[[Category: Patel, S B.]]
+[[Category: Patel SB]]
-[[Category: Ramachandran, C.]]
+[[Category: Ramachandran C]]
-[[Category: Scapin, G.]]
+[[Category: Scapin G]]
-[[Category: Skorey, K.]]
+[[Category: Skorey K]]
-[[Category: Therien, M.]]
+[[Category: Therien M]]
-[[Category: Waddleton, D.]]
+[[Category: Waddleton D]]
-[[Category: Wang, Q.]]
+[[Category: Wang Q]]
-[[Category: Phosphatase]]
-[[Category: Secondary binding site]]
-[[Category: Selectivity]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Feb 17 10:36:20 2009''