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| | <StructureSection load='1b48' size='340' side='right'caption='[[1b48]], [[Resolution|resolution]] 2.60Å' scene=''> | | <StructureSection load='1b48' size='340' side='right'caption='[[1b48]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1b48]] is a 2 chain structure with sequence from [https://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=1B48 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1B48 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1b48]] 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=1B48 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1B48 FirstGlance]. <br> |
| - | </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>, <scene name='pdbligand=HAG:4-S-GLUTATHIONYL-5-PENTYL-TETRAHYDRO-FURAN-2-OL'>HAG</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]] 2.6Å</td></tr> |
| - | <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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=HAG:4-S-GLUTATHIONYL-5-PENTYL-TETRAHYDRO-FURAN-2-OL'>HAG</scene></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=1b48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b48 OCA], [https://pdbe.org/1b48 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1b48 RCSB], [https://www.ebi.ac.uk/pdbsum/1b48 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1b48 ProSAT]</span></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=1b48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1b48 OCA], [https://pdbe.org/1b48 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1b48 RCSB], [https://www.ebi.ac.uk/pdbsum/1b48 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1b48 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/GSTA4_MOUSE GSTA4_MOUSE]] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
| + | [https://www.uniprot.org/uniprot/GSTA4_MOUSE GSTA4_MOUSE] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glutathione transferase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Ji, X]] | + | [[Category: Ji X]] |
| - | [[Category: Xiao, B]] | + | [[Category: Xiao B]] |
| - | [[Category: Zimniak, P]] | + | [[Category: Zimniak P]] |
| - | [[Category: Glutathione s-transferase]]
| + | |
| - | [[Category: Gst]]
| + | |
| - | [[Category: Subunit cooperativity]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
GSTA4_MOUSE Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
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
mGSTA4-4, a murine glutathione S-transferase (GST) exhibiting high activity in conjugating the lipid peroxidation product 4-hydroxynon-2-enal (4-HNE) with glutathione (GSH), was crystallized in complex with the GSH conjugate of 4-HNE (GS-Hna). The structure has been solved at 2.6 A resolution, which reveals that the active site of one subunit of the dimeric enzyme binds GS-Hna, whereas the other binds GSH. A marked asymmetry between the two subunits is evident. Most noticeable are the differences in the conformation of arginine residues 69 and 15. In all GST structures published previously, the guanidino groups of R69 residues from both subunits stack at the dimer interface and are related by a (pseudo-) 2-fold axis. In the present structure of mGSTA4-4, however, the two R69 side chains point in opposite directions, although their guanidino groups remain in contact. In the subunit with bound GSH, R69 also interacts with R15, and the guanidino group of R15 points away from the active site, whereas in the subunit that binds GS-Hna, R15 pivots into the active site, which breaks its interaction with R69. According to our previous results [Nanduri et al. (1997) Arch. Biochem. Biophys. 335, 305-310], the availability of R15 in the active site assists the conjugation of 4-HNE with GSH. We propose a model for the catalytic mechanism of mGSTA4-4 in conjugating 4-HNE with GSH-i.e., the guanidino group of R15 is available in the active site of only one subunit at any given time and the stacked pair of R69 residues act as a switch that couples the concerted movement of the two R15 side chains. The alternate occupancy of 4-HNE in the two subunits has been confirmed by our kinetic analysis that shows the negative cooperativity of mGSTA4-4 for 4-HNE. Disruption of the signaling between the subunits by mutating the R69 residues released the negative cooperativity with 4-HNE.
Crystal structure of a murine glutathione S-transferase in complex with a glutathione conjugate of 4-hydroxynon-2-enal in one subunit and glutathione in the other: evidence of signaling across the dimer interface.,Xiao B, Singh SP, Nanduri B, Awasthi YC, Zimniak P, Ji X Biochemistry. 1999 Sep 14;38(37):11887-94. PMID:10508391[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Xiao B, Singh SP, Nanduri B, Awasthi YC, Zimniak P, Ji X. Crystal structure of a murine glutathione S-transferase in complex with a glutathione conjugate of 4-hydroxynon-2-enal in one subunit and glutathione in the other: evidence of signaling across the dimer interface. Biochemistry. 1999 Sep 14;38(37):11887-94. PMID:10508391
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