View source for 6ssw


==Crystal structure of Human Microsomal Glutathione S-Transferase 2 in complex with an Inhibitor Glutathione sulfonic acid==
<StructureSection load='6ssw' size='340' side='right'caption='[[6ssw]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6ssw]] is a 3 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=6SSW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6SSW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTS:GLUTATHIONE+SULFONIC+ACID'>GTS</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=6ssw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ssw OCA], [https://pdbe.org/6ssw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ssw RCSB], [https://www.ebi.ac.uk/pdbsum/6ssw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ssw ProSAT]</span></td></tr>
</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> 
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6ssw" style="background-color:#fffaf0;"></div>

==See Also==
*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Haeggstrom JZ]]
[[Category: Thulasingam M]]