3gur

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{{Seed}}
 
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[[Image:3gur.jpg|left|200px]]
 
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==Crystal Structure of mu class glutathione S-transferase (GSTM2-2) in complex with glutathione and 6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX)==
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The line below this paragraph, containing "STRUCTURE_3gur", creates the "Structure Box" on the page.
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<StructureSection load='3gur' size='340' side='right'caption='[[3gur]], [[Resolution|resolution]] 2.50&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'>[[3gur]] is a 4 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=3GUR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GUR 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]] 2.5&#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=BYG:L-GAMMA-GLUTAMYL-S-{(4R)-4-[(6-HYDROXYHEXYL)SULFANYL]-7-NITRO-4,5-DIHYDRO-2,1,3-BENZOXADIAZOL-4-YL}-L-CYSTEINYLGLYCINE'>BYG</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene></td></tr>
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{{STRUCTURE_3gur| PDB=3gur | 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=3gur FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gur OCA], [https://pdbe.org/3gur PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gur RCSB], [https://www.ebi.ac.uk/pdbsum/3gur PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gur ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/GSTM2_HUMAN GSTM2_HUMAN] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.<ref>PMID:16549767</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/gu/3gur_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=3gur 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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Glutathione S-transferases (GST) constitute a superfamily of enzymes with diversified functions including detoxification from xenobiotics. In many human cancers, Pi class GST (GSTP1-1) is overexpressed and contributes to multidrug resistance by conjugating chemotherapeutics. In addition, GSTP1-1 displays antiapoptotic activity by interacting with c-Jun NH(2)-terminal kinase, a key regulator of apoptosis. Therefore, GSTP1-1 is considered a promising target for pharmaceutical treatment. Recently, a potent inhibitor of GSTs, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX), was identified and tested on several tumor cell lines demonstrating high antiproliferative activity. To establish the structural basis of NBDHEX activity, we determined the crystal structure of NBDHEX bound to either GSTP1-1 or GSTM2-2 (mu class). NBDHEX in both cases binds to the H-site but occupies different positions. Furthermore, the compound is covalently attached to the GSH sulfur in the GSTM2-2 crystal, forming a sigma-complex, although it is bound but not conjugated in the GSTP1-1 crystal. Several differences in the H-sites of the two isozymes determine the higher affinity of NBDHEX for GSTM2-2 with respect to GSTP1-1. One such difference is the presence of Ile(104) in GSTP1-1 close to the bound NBDHEX, whereas the corresponding position is occupied by an alanine in GSTM2-2. Mutation of Ile(104) into valine is a frequent GSTP1-1 polymorphism and we show here that the Ile(104)Val and Ile(104)Ala variants display a 4-fold higher affinity for the compound. Remarkably, the GSTP1-1/Ile(104)Ala structure in complex with NBDHEX shows a considerable shift of the compound inside the H-site. These data might be useful for the development of new anticancer compounds.
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===Crystal Structure of mu class glutathione S-transferase (GSTM2-2) in complex with glutathione and 6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX)===
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Structural basis for the binding of the anticancer compound 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol to human glutathione s-transferases.,Federici L, Lo Sterzo C, Pezzola S, Di Matteo A, Scaloni F, Federici G, Caccuri AM Cancer Res. 2009 Oct 15;69(20):8025-34. Epub 2009 Oct 6. PMID:19808963<ref>PMID:19808963</ref>
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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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<div class="pdbe-citations 3gur" style="background-color:#fffaf0;"></div>
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==See Also==
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The line below this paragraph, {{ABSTRACT_PUBMED_19808963}}, adds the Publication Abstract to the page
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*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
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(as it appears on PubMed at http://www.pubmed.gov), where 19808963 is the PubMed ID number.
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== References ==
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<references/>
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{{ABSTRACT_PUBMED_19808963}}
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__TOC__
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</StructureSection>
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==About this Structure==
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3GUR is a 4 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=3GUR OCA].
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==Reference==
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<ref group="xtra">PMID:19808963</ref><references group="xtra"/>
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[[Category: Glutathione transferase]]
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Caccuri, A M.]]
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[[Category: Large Structures]]
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[[Category: Federici, G.]]
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[[Category: Caccuri AM]]
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[[Category: Federici, L.]]
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[[Category: Di Matteo A]]
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[[Category: Matteo, A Di.]]
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[[Category: Federici G]]
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[[Category: Scaloni, F.]]
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[[Category: Federici L]]
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[[Category: Sterzo, C Lo.]]
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[[Category: Lo Sterzo C]]
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[[Category: Cytoplasm]]
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[[Category: Scaloni F]]
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[[Category: Gstm2-2/inhibitor complex]]
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[[Category: Polymorphism]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Oct 28 13:25:39 2009''
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Current revision

Crystal Structure of mu class glutathione S-transferase (GSTM2-2) in complex with glutathione and 6-(7-Nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol (NBDHEX)

PDB ID 3gur

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