2f3m: Difference between revisions
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==Structure of human GLUTATHIONE S-TRANSFERASE M1A-1A complexed with 1-(S-(GLUTATHIONYL)-2,4,6-TRINITROCYCLOHEXADIENATE ANION== | ==Structure of human GLUTATHIONE S-TRANSFERASE M1A-1A complexed with 1-(S-(GLUTATHIONYL)-2,4,6-TRINITROCYCLOHEXADIENATE ANION== | ||
<StructureSection load='2f3m' size='340' side='right' caption='[[2f3m]], [[Resolution|resolution]] 2.70Å' scene=''> | <StructureSection load='2f3m' size='340' side='right'caption='[[2f3m]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2f3m]] is a 6 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2f3m]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F3M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2F3M FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GTD:1-(S-GLUTATHIONYL)-2,4,6-TRINITROCYCLOHEXA-2,5-DIENE'>GTD</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTD:1-(S-GLUTATHIONYL)-2,4,6-TRINITROCYCLOHEXA-2,5-DIENE'>GTD</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1gtu|1gtu]], [[1xw6|1xw6]], [[1xwk|1xwk]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1gtu|1gtu]], [[1xw6|1xw6]], [[1xwk|1xwk]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GSTM1, GST1 ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GSTM1, GST1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Glutathione_transferase Glutathione transferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.18 2.5.1.18] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2f3m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f3m OCA], [https://pdbe.org/2f3m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f3m RCSB], [https://www.ebi.ac.uk/pdbsum/2f3m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f3m ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/GSTM1_HUMAN GSTM1_HUMAN]] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.<ref>PMID:16548513</ref> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
Check<jmol> | Check<jmol> | ||
<jmolCheckbox> | <jmolCheckbox> | ||
<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f3/2f3m_consurf.spt"</scriptWhenChecked> | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/f3/2f3m_consurf.spt"</scriptWhenChecked> | ||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | ||
<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
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</div> | </div> | ||
<div class="pdbe-citations 2f3m" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 2f3m" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
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[[Category: Glutathione transferase]] | [[Category: Glutathione transferase]] | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Almo, S C]] | [[Category: Almo, S C]] | ||
[[Category: Listowsky, I]] | [[Category: Listowsky, I]] | ||
Revision as of 13:37, 17 February 2021
Structure of human GLUTATHIONE S-TRANSFERASE M1A-1A complexed with 1-(S-(GLUTATHIONYL)-2,4,6-TRINITROCYCLOHEXADIENATE ANIONStructure of human GLUTATHIONE S-TRANSFERASE M1A-1A complexed with 1-(S-(GLUTATHIONYL)-2,4,6-TRINITROCYCLOHEXADIENATE ANION
Structural highlights
Function[GSTM1_HUMAN] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedAn active site His107 residue distinguishes human glutathione S-transferase hGSTM1-1 from other mammalian Mu-class GSTs. The crystal structure of hGSTM1a-1a with bound glutathione (GSH) was solved to 1.9 A resolution, and site-directed mutagenesis supports the conclusion that a proton transfer occurs in which bound water at the catalytic site acts as a primary proton acceptor from the GSH thiol group to transfer the proton to His107. The structure of the second substrate-binding site (H-site) was determined from hGSTM1a-1a complexed with 1-glutathionyl-2,4-dinitrobenzene (GS-DNB) formed by a reaction in the crystal between GSH and 1-chloro-2,4-dinitrobenzene (CDNB). In that structure, the GSH-binding site (G-site) is occupied by the GSH moiety of the product in the same configuration as that of the enzyme-GSH complex, and the dinitrobenzene ring is anchored between the side chains of Tyr6, Leu12, His107, Met108, and Tyr115. This orientation suggested a distinct transition state that was substantiated from the structure of hGSTM1a-1a complexed with transition state analogue 1-S-(glutathionyl)-2,4,6-trinitrocyclohexadienate (Meisenheimer complex). Kinetic data for GSTM1a-1a indicate that kcat(CDNB) for the reaction is more than 3 times greater than kcat(FDNB), even though the nonenzymatic second-order rate constant is more than 50-fold greater for 1-fluoro-2,4-dinitrobenzene (FDNB), and the product is the same for both substrates. In addition, Km(FDNB) is about 20 times less than Km(CDNB). The results are consistent with a mechanism in which the formation of the transition state is rate-limiting in the nucleophilic aromatic substitution reactions. Data obtained with active-site mutants support transition states in which Tyr115, Tyr6, and His107 side chains are involved in the stabilization of the Meisenheimer complex via interactions with the ortho nitro group of CDNB or FDNB and provide insight into the means by which GSTs adapt to accommodate different substrates. Transition state model and mechanism of nucleophilic aromatic substitution reactions catalyzed by human glutathione S-transferase M1a-1a.,Patskovsky Y, Patskovska L, Almo SC, Listowsky I Biochemistry. 2006 Mar 28;45(12):3852-62. PMID:16548513[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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