6ssu
From Proteopedia
(Difference between revisions)
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==Crystal structure of Human Microsomal Glutathione S-Transferase 2 in complex with co-substrate Glutathione== | ==Crystal structure of Human Microsomal Glutathione S-Transferase 2 in complex with co-substrate Glutathione== | ||
| - | <StructureSection load='6ssu' size='340' side='right'caption='[[6ssu]]' scene=''> | + | <StructureSection load='6ssu' size='340' side='right'caption='[[6ssu]], [[Resolution|resolution]] 2.50Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6SSU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SSU FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ssu]] is a 3 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=6SSU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SSU FirstGlance]. <br> |
| - | </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=6ssu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ssu OCA], [https://pdbe.org/6ssu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ssu RCSB], [https://www.ebi.ac.uk/pdbsum/6ssu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ssu ProSAT]</span></td></tr> | + | </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=NO3:NITRATE+ION'>NO3</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MGST2, GST2 ([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'>[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'>[https://proteopedia.org/fgij/fg.htm?mol=6ssu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ssu OCA], [https://pdbe.org/6ssu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ssu RCSB], [https://www.ebi.ac.uk/pdbsum/6ssu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ssu ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/MGST2_HUMAN MGST2_HUMAN]] Catalyzes several different glutathione-dependent reactions (PubMed:8703034, PubMed:9278457, PubMed:23409838, PubMed:26656251, PubMed:26066610). Catalyzes the glutathione-dependent reduction of lipid hydroperoxides, such as 5-HPETE (PubMed:9278457, PubMed:23409838). Has glutathione transferase activity, toward xenobiotic electrophiles, such as 1-chloro-2, 4-dinitrobenzene (CDNB) (PubMed:23409838, PubMed:8703034). Catalyzes also the conjugation of leukotriene A4 with reduced glutathione to form leukotriene C4 (LTC4) (PubMed:23409838, PubMed:26656251). Involved in oxidative DNA damage induced by ER stress and anticancer agents by activating LTC4 biosynthetic machinery in nonimmune cells (PubMed:26656251).<ref>PMID:23409838</ref> <ref>PMID:26066610</ref> <ref>PMID:26656251</ref> <ref>PMID:8703034</ref> <ref>PMID:9278457</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Microsomal glutathione S-transferase 2 (MGST2) produces leukotriene C4, key for intracrine signaling of endoplasmic reticulum (ER) stress, oxidative DNA damage and cell death. MGST2 trimer restricts catalysis to only one out of three active sites at a time, but the molecular basis is unknown. Here, we present crystal structures of human MGST2 combined with biochemical and computational evidence for a concerted mechanism, involving local unfolding coupled to global conformational changes that regulate catalysis. Furthermore, synchronized changes in the biconical central pore modulate the hydrophobicity and control solvent influx to optimize reaction conditions at the active site. These unique mechanistic insights pertain to other, structurally related, drug targets. | ||
| + | |||
| + | Crystal structures of human MGST2 reveal synchronized conformational changes regulating catalysis.,Thulasingam M, Orellana L, Nji E, Ahmad S, Rinaldo-Matthis A, Haeggstrom JZ Nat Commun. 2021 Mar 19;12(1):1728. doi: 10.1038/s41467-021-21924-8. PMID:33741927<ref>PMID:33741927</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6ssu" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Glutathione transferase]] | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Haeggstrom | + | [[Category: Haeggstrom, J Z]] |
| - | [[Category: Thulasingam M]] | + | [[Category: Thulasingam, M]] |
| + | [[Category: Er membrane protein]] | ||
| + | [[Category: Integral membrane enzyme]] | ||
| + | [[Category: Mapeg]] | ||
| + | [[Category: Mgst2]] | ||
| + | [[Category: Transferase]] | ||
Revision as of 07:03, 7 April 2021
Crystal structure of Human Microsomal Glutathione S-Transferase 2 in complex with co-substrate Glutathione
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