2pgt

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(New page: 200px<br /> <applet load="2pgt" size="450" color="white" frame="true" align="right" spinBox="true" caption="2pgt, resolution 1.90&Aring;" /> '''CRYSTAL STRUCTURE O...)
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[[Image:2pgt.gif|left|200px]]<br />
 
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<applet load="2pgt" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2pgt, resolution 1.90&Aring;" />
 
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'''CRYSTAL STRUCTURE OF HUMAN GLUTATHIONE S-TRANSFERASE P1-1[V104] COMPLEXED WITH (9R,10R)-9-(S-GLUTATHIONYL)-10-HYDROXY-9,10-DIHYDROPHENANTHRENE'''<br />
 
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==Overview==
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==CRYSTAL STRUCTURE OF HUMAN GLUTATHIONE S-TRANSFERASE P1-1[V104] COMPLEXED WITH (9R,10R)-9-(S-GLUTATHIONYL)-10-HYDROXY-9,10-DIHYDROPHENANTHRENE==
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Complex structures of a naturally occurring variant of human class pi, glutathione S-transferase 1-1 (hGSTP1-1) with either S-hexylglutathione or, (9R,10R)-9-(S-glutathionyl)-10-hydroxy-9, 10-dihydrophenanthrene, [(9R,10R)-GSPhen] have been determined at resolutions of 1.8 and 1.9 A, respectively. The crystal structures reveal that the xenobiotic, substrate-binding site (H-site) is located at a position similar to that, observed in class mu GST 1-1 from rat liver (rGSTM1-1). In rGSTM1-1, the, H-site is a hydrophobic cavity defined by the side chains of Y6, W7, V9, L12, I111, Y115, F208, and S209. In hGSTP1-1, the cavity is approximately, half hydrophobic and half hydrophilic and is defined by the side chains of, Y7, F8, V10, R13, V104, Y108, N204, and G205 and five water molecules. A, hydrogen bond network connects the five water molecules and the side, chains of R13 and N204. V104 is positioned such that the introduction of a, methyl group (the result of the V104I mutation) disturbs the H-site water, structure and alters the substrate-binding properties of the isozyme. The, hydroxyl group of Y7 forms a hydrogen bond (3.2 A) with the sulfur atom of, the product. There is a short hydrogen bond (2.5 A) between Y108 (OH) and, (9R, 10R)-GSPhen (O5), indicating the hydroxyl group of Y108 as an, electrophilic participant in the addition of glutathione to epoxides. An, N-(2-hydroxethyl)piperazine-N'-2-ethanesulfonic acid (HEPES) molecule is, found in the cavity between beta2 and alphaI. The location and properties, of this HEPES-binding site fit a possible non-substrate-binding site that, is involved in noncompetitive inhibition of the enzyme.
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<StructureSection load='2pgt' size='340' side='right'caption='[[2pgt]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2pgt]] 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=2PGT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PGT 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]] 1.9&#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=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GPR:(9R,10R)-9-(S-GLUTATHIONYL)-10-HYDROXY-9,10-DIHYDROPHENANTHRENE'>GPR</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=2pgt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pgt OCA], [https://pdbe.org/2pgt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pgt RCSB], [https://www.ebi.ac.uk/pdbsum/2pgt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pgt ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GSTP1_HUMAN GSTP1_HUMAN] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.<ref>PMID:21668448</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/pg/2pgt_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=2pgt 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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Complex structures of a naturally occurring variant of human class pi glutathione S-transferase 1-1 (hGSTP1-1) with either S-hexylglutathione or (9R,10R)-9-(S-glutathionyl)-10-hydroxy-9, 10-dihydrophenanthrene [(9R,10R)-GSPhen] have been determined at resolutions of 1.8 and 1.9 A, respectively. The crystal structures reveal that the xenobiotic substrate-binding site (H-site) is located at a position similar to that observed in class mu GST 1-1 from rat liver (rGSTM1-1). In rGSTM1-1, the H-site is a hydrophobic cavity defined by the side chains of Y6, W7, V9, L12, I111, Y115, F208, and S209. In hGSTP1-1, the cavity is approximately half hydrophobic and half hydrophilic and is defined by the side chains of Y7, F8, V10, R13, V104, Y108, N204, and G205 and five water molecules. A hydrogen bond network connects the five water molecules and the side chains of R13 and N204. V104 is positioned such that the introduction of a methyl group (the result of the V104I mutation) disturbs the H-site water structure and alters the substrate-binding properties of the isozyme. The hydroxyl group of Y7 forms a hydrogen bond (3.2 A) with the sulfur atom of the product. There is a short hydrogen bond (2.5 A) between Y108 (OH) and (9R, 10R)-GSPhen (O5), indicating the hydroxyl group of Y108 as an electrophilic participant in the addition of glutathione to epoxides. An N-(2-hydroxethyl)piperazine-N'-2-ethanesulfonic acid (HEPES) molecule is found in the cavity between beta2 and alphaI. The location and properties of this HEPES-binding site fit a possible non-substrate-binding site that is involved in noncompetitive inhibition of the enzyme.
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==About this Structure==
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Structure and function of the xenobiotic substrate-binding site and location of a potential non-substrate-binding site in a class pi glutathione S-transferase.,Ji X, Tordova M, O'Donnell R, Parsons JF, Hayden JB, Gilliland GL, Zimniak P Biochemistry. 1997 Aug 12;36(32):9690-702. PMID:9245401<ref>PMID:9245401</ref>
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2PGT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with SO4, GPR and EPE as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Glutathione_transferase Glutathione transferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.18 2.5.1.18] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2PGT OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Structure and function of the xenobiotic substrate-binding site and location of a potential non-substrate-binding site in a class pi glutathione S-transferase., Ji X, Tordova M, O'Donnell R, Parsons JF, Hayden JB, Gilliland GL, Zimniak P, Biochemistry. 1997 Aug 12;36(32):9690-702. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9245401 9245401]
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</div>
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[[Category: Glutathione transferase]]
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<div class="pdbe-citations 2pgt" style="background-color:#fffaf0;"></div>
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[[Category: Homo sapiens]]
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[[Category: Single protein]]
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[[Category: Ji, X.]]
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[[Category: EPE]]
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[[Category: GPR]]
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[[Category: SO4]]
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[[Category: detoxification]]
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[[Category: hgstp1-1[v104]]]
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[[Category: pi class]]
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[[Category: transferase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:23:42 2007''
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==See Also==
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*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Homo sapiens]]
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[[Category: Large Structures]]
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[[Category: Ji X]]

Current revision

CRYSTAL STRUCTURE OF HUMAN GLUTATHIONE S-TRANSFERASE P1-1[V104] COMPLEXED WITH (9R,10R)-9-(S-GLUTATHIONYL)-10-HYDROXY-9,10-DIHYDROPHENANTHRENE

PDB ID 2pgt

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