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| | ==1.8 Angstroms molecular structure of mouse liver glutathione S-transferase mutant C47A complexed with S-(P-nitrobenzyl)glutathione== | | ==1.8 Angstroms molecular structure of mouse liver glutathione S-transferase mutant C47A complexed with S-(P-nitrobenzyl)glutathione== |
| - | <StructureSection load='3o76' size='340' side='right' caption='[[3o76]], [[Resolution|resolution]] 1.77Å' scene=''> | + | <StructureSection load='3o76' size='340' side='right'caption='[[3o76]], [[Resolution|resolution]] 1.77Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3o76]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O76 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3O76 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3o76]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3O76 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3O76 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GTB:S-(P-NITROBENZYL)GLUTATHIONE'>GTB</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]] 1.77Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1glq|1glq]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTB:S-(P-NITROBENZYL)GLUTATHIONE'>GTB</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Gstp1, Gstpib ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=3o76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o76 OCA], [https://pdbe.org/3o76 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3o76 RCSB], [https://www.ebi.ac.uk/pdbsum/3o76 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3o76 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>
| + | |
| - | <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=3o76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3o76 OCA], [http://pdbe.org/3o76 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3o76 RCSB], [http://www.ebi.ac.uk/pdbsum/3o76 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3o76 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GSTP1_MOUSE GSTP1_MOUSE]] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Can metabolize 1-chloro-2,4-dinitrobenzene. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration (By similarity). | + | [https://www.uniprot.org/uniprot/GSTP1_MOUSE GSTP1_MOUSE] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Can metabolize 1-chloro-2,4-dinitrobenzene. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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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: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Canals, A]] | + | [[Category: Canals A]] |
| - | [[Category: Coll, M]] | + | [[Category: Coll M]] |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
GSTP1_MOUSE Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Can metabolize 1-chloro-2,4-dinitrobenzene. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration (By similarity).
Publication Abstract from PubMed
Mouse liver glutathione transferase P1-1 has three cysteine residues at positions 14, 47 and 169. We have constructed the single, double and triple cysteine to alanine mutants to define the behaviour of all three thiols. We confirm that C47 is the 'fast' thiol (pK 7.4), and define C169 as the alkaline reactive residue with a pK(a) of 8.6. Only a small proportion of C14 is reactive with 5,5'-dithiobis-(2-nitrobenoic acid) (DTNB) at pH 9 in the C47A/C169A double mutant. The native enzyme and the C169A mutant exhibited Michaelis-Menten kinetics, but all other thiol to alanine mutants exhibited sigmoidal kinetics to varying degrees. The C169A mutant exhibited 'ping pong' kinetics, consistent with a mechanism whereby liberation of a proton from a reduced enzyme-glutathione (GSH) complex to form an enzyme-GS(-) (unprotonated) complex is essentially irreversible. Intriguingly, similar behaviour has recently been reported for a mutant of the yeast prion Ure2p. This cooperative behaviour is 'mirrored' in the crystal structure of the C47A mutant, which binds the p-nitrobenzyl moiety of p-nitrobenzyglutathione in distinct orientations in the two crystallographic subunits. The asymmetry seen in this structure for product binding is associated with absence of a water molecule W0 in the standard wild-type conformation of product binding that is clearly identifiable in the new structure, which may represent a structural model for binding of incoming GSH prior to displacement of W0. Elimination of W0 as a hydroxonium ion may be the mechanism for the initial proton extrusion from the active site.
Site-directed mutagenesis of mouse glutathione transferase P1-1 unlocks masked cooperativity, introduces a novel mechanism for 'ping pong' kinetic behaviour, and provides further structural evidence for participation of a water molecule in proton abstraction from glutathione.,McManus G, Costa M, Canals A, Coll M, Mantle TJ FEBS J. 2011 Jan;278(2):273-81. doi: 10.1111/j.1742-4658.2010.07944.x., Epub 2010 Dec 6. PMID:21134126[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ McManus G, Costa M, Canals A, Coll M, Mantle TJ. Site-directed mutagenesis of mouse glutathione transferase P1-1 unlocks masked cooperativity, introduces a novel mechanism for 'ping pong' kinetic behaviour, and provides further structural evidence for participation of a water molecule in proton abstraction from glutathione. FEBS J. 2011 Jan;278(2):273-81. doi: 10.1111/j.1742-4658.2010.07944.x., Epub 2010 Dec 6. PMID:21134126 doi:10.1111/j.1742-4658.2010.07944.x
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