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| | <StructureSection load='5jcw' size='340' side='right'caption='[[5jcw]], [[Resolution|resolution]] 1.94Å' scene=''> | | <StructureSection load='5jcw' size='340' side='right'caption='[[5jcw]], [[Resolution|resolution]] 1.94Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5jcw]] 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=5JCW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5JCW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5jcw]] 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=5JCW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JCW FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=GVX:L-GAMMA-GLUTAMYL-S-[(2-PHENYLETHYL)CARBAMOTHIOYL]-L-CYSTEINYLGLYCINE'>GVX</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</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]] 1.945Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5jcu|5jcu]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=GVX:L-GAMMA-GLUTAMYL-S-[(2-PHENYLETHYL)CARBAMOTHIOYL]-L-CYSTEINYLGLYCINE'>GVX</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GSTP1, FAEES3, GST3 ([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=5jcw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jcw OCA], [https://pdbe.org/5jcw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jcw RCSB], [https://www.ebi.ac.uk/pdbsum/5jcw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jcw 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://proteopedia.org/fgij/fg.htm?mol=5jcw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jcw OCA], [http://pdbe.org/5jcw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jcw RCSB], [http://www.ebi.ac.uk/pdbsum/5jcw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jcw ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/GSTP1_HUMAN GSTP1_HUMAN]] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.<ref>PMID:21668448</ref> | + | [https://www.uniprot.org/uniprot/GSTP1_HUMAN GSTP1_HUMAN] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.<ref>PMID:21668448</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glutathione transferase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ji, X]] | + | [[Category: Ji X]] |
| - | [[Category: Kumari, V]] | + | [[Category: Kumari V]] |
| - | [[Category: Glutathione adduct]]
| + | |
| - | [[Category: Gst]]
| + | |
| - | [[Category: Peitc]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
5jcw is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.945Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
GSTP1_HUMAN Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.[1]
Publication Abstract from PubMed
Dietary isothiocyanates abundant as glucosinolate precursors in many edible cruciferous vegetables are effective for prevention of cancer in chemically-induced and transgenic rodent models. Some of these agents, including phenethyl isothiocyanate (PEITC), have already advanced to clinical investigations. The primary route of isothiocyanate metabolism is its conjugation with glutathione (GSH), a reaction catalyzed by glutathione S-transferase (GST). The pi class GST of subunit type 1 (hGSTP1) is much more effective than the alpha class GST of subunit type 1 (hGSTA1) in catalyzing the conjugation. Here, we report the crystal structures of hGSTP1 and hGSTA1 each in complex with the GSH adduct of PEITC. We find that PEITC also covalently modifies the cysteine side chains of GST, which irreversibly inhibits enzymatic activity.
Irreversible Inhibition of Glutathione S-Transferase by Phenethyl Isothiocyanate (PEITC), a Dietary Cancer Chemopreventive Phytochemical.,Kumari V, Dyba MA, Holland RJ, Liang YH, Singh SV, Ji X PLoS One. 2016 Sep 29;11(9):e0163821. doi: 10.1371/journal.pone.0163821., eCollection 2016. PMID:27684484[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sun KH, Chang KH, Clawson S, Ghosh S, Mirzaei H, Regnier F, Shah K. Glutathione-S-transferase P1 is a critical regulator of Cdk5 kinase activity. J Neurochem. 2011 Sep;118(5):902-14. doi: 10.1111/j.1471-4159.2011.07343.x. Epub , 2011 Jul 8. PMID:21668448 doi:10.1111/j.1471-4159.2011.07343.x
- ↑ Kumari V, Dyba MA, Holland RJ, Liang YH, Singh SV, Ji X. Irreversible Inhibition of Glutathione S-Transferase by Phenethyl Isothiocyanate (PEITC), a Dietary Cancer Chemopreventive Phytochemical. PLoS One. 2016 Sep 29;11(9):e0163821. doi: 10.1371/journal.pone.0163821., eCollection 2016. PMID:27684484 doi:http://dx.doi.org/10.1371/journal.pone.0163821
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