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| | ==Crystal Structure of hGSTA3-3 in Complex with Glutathione== | | ==Crystal Structure of hGSTA3-3 in Complex with Glutathione== |
| - | <StructureSection load='1tdi' size='340' side='right' caption='[[1tdi]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='1tdi' size='340' side='right'caption='[[1tdi]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1tdi]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1TDI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1TDI FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1tdi]] 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=1TDI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1TDI FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1guh|1guh]], [[1gse|1gse]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GSTA3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=1tdi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tdi OCA], [https://pdbe.org/1tdi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1tdi RCSB], [https://www.ebi.ac.uk/pdbsum/1tdi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1tdi ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1tdi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1tdi OCA], [http://pdbe.org/1tdi PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1tdi RCSB], [http://www.ebi.ac.uk/pdbsum/1tdi PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GSTA3_HUMAN GSTA3_HUMAN]] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Catalyzes isomerization reactions that contribute to the biosynthesis of steroid hormones. Efficiently catalyze obligatory double-bond isomerizations of delta(5)-androstene-3,17-dione and delta(5)-pregnene-3,20-dione, precursors to testosterone and progesterone, respectively.<ref>PMID:15595823</ref> <ref>PMID:20083122</ref> | + | [https://www.uniprot.org/uniprot/GSTA3_HUMAN GSTA3_HUMAN] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Catalyzes isomerization reactions that contribute to the biosynthesis of steroid hormones. Efficiently catalyze obligatory double-bond isomerizations of delta(5)-androstene-3,17-dione and delta(5)-pregnene-3,20-dione, precursors to testosterone and progesterone, respectively.<ref>PMID:15595823</ref> <ref>PMID:20083122</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/td/1tdi_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/td/1tdi_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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| | ==See Also== | | ==See Also== |
| - | *[[Glutathione S-transferase|Glutathione S-transferase]] | + | *[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glutathione transferase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Gu, Y]] | + | [[Category: Gu Y]] |
| - | [[Category: Guo, J]] | + | [[Category: Guo J]] |
| - | [[Category: Ji, X]] | + | [[Category: Ji X]] |
| - | [[Category: Pal, A]] | + | [[Category: Pal A]] |
| - | [[Category: Pan, S S]] | + | [[Category: Pan SS]] |
| - | [[Category: Singh, S V]] | + | [[Category: Singh SV]] |
| - | [[Category: Zimniak, P]] | + | [[Category: Zimniak P]] |
| - | [[Category: Gst]]
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| - | [[Category: Hgsta3-3]]
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| - | [[Category: Steroid isomerase]]
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| - | [[Category: Transferase]]
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| Structural highlights
Function
GSTA3_HUMAN Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Catalyzes isomerization reactions that contribute to the biosynthesis of steroid hormones. Efficiently catalyze obligatory double-bond isomerizations of delta(5)-androstene-3,17-dione and delta(5)-pregnene-3,20-dione, precursors to testosterone and progesterone, respectively.[1] [2]
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 PubMed
The crystal structure of human class alpha glutathione (GSH) S-transferase A3-3 (hGSTA3-3) in complex with GSH was determined at 2.4 A. Despite considerable amino acid sequence identity with other human class alpha GSTs (e.g., hGSTA1-1), hGSTA3-3 is unique due to its exceptionally high steroid double bond isomerase activity for the transformation of Delta(5)-androstene-3,17-dione (Delta(5)-AD) to Delta(4)-androstene-3,17-dione. A comparative analysis of the active centers of hGSTA1-1 and hGSTA3-3 reveals that residues in positions 12 and 208 may contribute to their disparate isomerase activity toward Delta(5)-AD. Substitution of these two residues of hGSTA3-3 with the corresponding residues in hGSTA1-1 followed by kinetic characterization of the wild-type and the mutant enzymes supported this prediction. On the basis of our model of the hGSTA3-3.GSH.Delta(5)-AD ternary complex and available biochemical data, we propose that the thiolate group of deprotonated GSH (GS(-)) serves as a base to initiate the reaction by accepting a proton from the steroid and the nonionized hydroxyl group of catalytic residue Y9 (HO-Y9) functions as part of a proton-conducting wire to transfer a proton back to the steroid. Residue R15 may function to stabilize the deprotonated thiolate group of GSH (GS(-)), and a GSH-bound water molecule may donate a hydrogen bond to the 3-keto group of Delta(5)-AD and thus help the thiolate of GS(-) to initiate the proton transfer and the subsequent stabilization of the reaction intermediate.
Crystal structure of human glutathione S-transferase A3-3 and mechanistic implications for its high steroid isomerase activity.,Gu Y, Guo J, Pal A, Pan SS, Zimniak P, Singh SV, Ji X Biochemistry. 2004 Dec 21;43(50):15673-9. PMID:15595823[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gu Y, Guo J, Pal A, Pan SS, Zimniak P, Singh SV, Ji X. Crystal structure of human glutathione S-transferase A3-3 and mechanistic implications for its high steroid isomerase activity. Biochemistry. 2004 Dec 21;43(50):15673-9. PMID:15595823 doi:10.1021/bi048757g
- ↑ Tars K, Olin B, Mannervik B. Structural basis for featuring of steroid isomerase activity in alpha class glutathione transferases. J Mol Biol. 2010 Mar 19;397(1):332-40. Epub 2010 Jan 18. PMID:20083122 doi:10.1016/j.jmb.2010.01.023
- ↑ Gu Y, Guo J, Pal A, Pan SS, Zimniak P, Singh SV, Ji X. Crystal structure of human glutathione S-transferase A3-3 and mechanistic implications for its high steroid isomerase activity. Biochemistry. 2004 Dec 21;43(50):15673-9. PMID:15595823 doi:10.1021/bi048757g
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