1ony: Difference between revisions

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-[[Image:1ony.jpg|left|200px]]
- {{Structure
+==Oxalyl-Aryl-Amino Benzoic Acid inhibitors of PTP1B, compound 17==
-|PDB= 1ony |SIZE=350|CAPTION= <scene name='initialview01'>1ony</scene>, resolution 2.15&Aring;
+<StructureSection load='1ony' size='340' side='right'caption='[[1ony]], [[Resolution|resolution]] 2.15&Aring;' scene=''>
-|SITE=
+== Structural highlights ==
-|LIGAND= <scene name='pdbligand=588:2-{[2-(2-CARBAMOYL-VINYL)-4-(2-METHANESULFONYLAMINO-2-PENTYLCARBAMOYL-ETHYL)-PHENYL]-OXALYL-AMINO}-BENZOIC ACID'>588</scene>
+<table><tr><td colspan='2'>[[1ony]] 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=1ONY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1ONY FirstGlance]. <br>
-|ACTIVITY= [http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48]
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.15&#8491;</td></tr>
-|GENE= PTPN1 OR PTP1B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=588:2-{[2-(2-CARBAMOYL-VINYL)-4-(2-METHANESULFONYLAMINO-2-PENTYLCARBAMOYL-ETHYL)-PHENYL]-OXALYL-AMINO}-BENZOIC+ACID'>588</scene></td></tr>
-}}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ony FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ony OCA], [https://pdbe.org/1ony PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ony RCSB], [https://www.ebi.ac.uk/pdbsum/1ony PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ony ProSAT]</span></td></tr>
+</table>
-'''Oxalyl-Aryl-Amino Benzoic Acid inhibitors of PTP1B, compound 17'''
+== 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 ==
-==Overview==
+[[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/on/1ony_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=1ony ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
 Protein Tyrosine phosphatase 1B (PTP1B) has been implicated as a key negative regulator of both insulin and leptin signaling pathways. Using an NMR-based screening approach with 15N- and 13C-labeled PTP1B, we have identified 2,3-dimethylphenyloxalylaminobenzoic acid (1) as a general, reversible, and competitive PTPase inhibitor. Structure-based approach guided by X-ray crystallography facilitated the development of 1 into a novel series of potent and selective PTP1B inhibitors occupying both the catalytic site and a portion of the noncatalytic, second phosphotyrosine binding site. Interestingly, oral biovailability has been observed in rats for some compounds. Furthermore, we demonstrated in vivo plasma glucose lowering effects with compound 12d in ob/ob mice.
-==Disease==
+Discovery and structure-activity relationship of oxalylarylaminobenzoic acids as inhibitors of protein tyrosine phosphatase 1B.,Liu G, Szczepankiewicz BG, Pei Z, Janowick DA, Xin Z, Hajduk PJ, Abad-Zapatero C, Liang H, Hutchins CW, Fesik SW, Ballaron SJ, Stashko MA, Lubben T, Mika AK, Zinker BA, Trevillyan JM, Jirousek MR J Med Chem. 2003 May 22;46(11):2093-103. PMID:12747781<ref>PMID:12747781</ref>
-Known diseases 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]]
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-ONY 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=1ONY OCA].
+</div>
+<div class="pdbe-citations 1ony" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Discovery and structure-activity relationship of oxalylarylaminobenzoic acids as inhibitors of protein tyrosine phosphatase 1B., Liu G, Szczepankiewicz BG, Pei Z, Janowick DA, Xin Z, Hajduk PJ, Abad-Zapatero C, Liang H, Hutchins CW, Fesik SW, Ballaron SJ, Stashko MA, Lubben T, Mika AK, Zinker BA, Trevillyan JM, Jirousek MR, J Med Chem. 2003 May 22;46(11):2093-103. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12747781 12747781]
+*[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Protein-tyrosine-phosphatase]]
+[[Category: Large Structures]]
-[[Category: Single protein]]
+[[Category: Abad-Zapatero C]]
-[[Category: Abad-Zapatero, C.]]
+[[Category: Ballaron SJ]]
-[[Category: Ballaron, S J.]]
+[[Category: Fesik SW]]
-[[Category: Fesik, S W.]]
+[[Category: Hadjuk PJ]]
-[[Category: Hadjuk, P J.]]
+[[Category: Hutchins CW]]
-[[Category: Hutchins, C W.]]
+[[Category: Janowich DA]]
-[[Category: Janowich, D A.]]
+[[Category: Jirousek MR]]
-[[Category: Jirousek, M R.]]
+[[Category: Liang H]]
-[[Category: Liang, H.]]
+[[Category: Liu G]]
-[[Category: Liu, G.]]
+[[Category: Lubben T]]
-[[Category: Lubben, T.]]
+[[Category: Mika AK]]
-[[Category: Mika, A K.]]
+[[Category: Pei Z]]
-[[Category: Pei, Z.]]
+[[Category: Stashko MA]]
-[[Category: Stashko, M A.]]
+[[Category: Szczepankiewicz BG]]
-[[Category: Szczepankiewicz, B G.]]
+[[Category: Trevillyan JM]]
-[[Category: Trevillyan, J M.]]
+[[Category: Xin Z]]
-[[Category: Xin, Z.]]
+[[Category: Zinker BA]]
-[[Category: Zinker, B A.]]
-[[Category: 588]]
-[[Category: oxalyl-aryl-amino benzoic acid inhibitor]]
-[[Category: protein tyrosine phosphatase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:13:23 2008''