8vou
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Human glutathione transferase M1-1 in complex with the adduct between glutathione and nitrooleic acid== | |
| + | <StructureSection load='8vou' size='340' side='right'caption='[[8vou]], [[Resolution|resolution]] 2.55Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8vou]] is a 4 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=8VOU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8VOU 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]] 2.55Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1AWW:(9~{R},10~{S})-9-[(2~{R})-2-[[(4~{S})-4-azanyl-5-oxidanyl-5-oxidanylidene-pentanoyl]amino]-3-(2-hydroxy-2-oxoethylamino)-3-oxidanylidene-propyl]sulfanyl-10-nitro-octadecanoic+acid'>A1AWW</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</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=8vou FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8vou OCA], [https://pdbe.org/8vou PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8vou RCSB], [https://www.ebi.ac.uk/pdbsum/8vou PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8vou ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/GSTM1_HUMAN GSTM1_HUMAN] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.<ref>PMID:16548513</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Nitroalkene fatty acids (NO(2)-FAs) are formed endogenously. They regulate cell signaling pathways and are being developed clinically to treat inflammatory diseases. NO(2)-FAs are electrophilic and form thioether adducts with glutathione (GSH), which are exported from cells. Glutathione transferases (GSTs), a superfamily of enzymes, contribute to the cellular detoxification of hydrophobic electrophiles by catalyzing their conjugation to GSH. Herein, we evaluated the capacity of five human GSTs (M1-1, M2-2, M4-4, A4-4, and P1-1) to catalyze the reaction between nitrooleic acid (NO(2)-OA) and GSH. The reaction was monitored by HPLC-ESI-MS/MS and catalytic activity was detected with hGSTs M1-1 and A4-4. Using stopped-flow spectrophotometry, a 1400 and 7500-fold increase in the apparent second-order rate constant was observed for hGST M1-1 and hGST A4-4, respectively, compared to the uncatalyzed reaction (pH 7.4, 25 degrees C), in part due to a higher availability of the thiolate. The crystal structure of hGST M1-1 in complex with the adduct was solved at 2.55 A resolution, revealing that the ligand was bound within the reaction center, and establishing a foundation to build a model of hGST A4-4 in complex with the adduct. A larger number of interactions between the enzyme and the fatty acid were observed for hGST A4-4 compared to hGST M1-1, probably contributing to the increased catalysis. Altogether, these results show, for the first time, that hGSTs can catalyze the reaction between GSH and NO(2)-FAs, likely affecting the signaling actions of these metabolites and expanding the repertoire of GST reactions. | ||
| - | + | Human glutathione transferases catalyze the reaction between glutathione and nitrooleic acid.,Steglich M, Larrieux N, Zeida A, Rizza JD, Salvatore SR, Bonilla M, Moller MN, Buschiazzo A, Alvarez B, Schopfer FJ, Turell L J Biol Chem. 2025 Feb 28:108362. doi: 10.1016/j.jbc.2025.108362. PMID:40024478<ref>PMID:40024478</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8vou" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Buschiazzo A]] | ||
| + | [[Category: Dalla Rizza J]] | ||
| + | [[Category: Larrieux N]] | ||
| + | [[Category: Steglich M]] | ||
| + | [[Category: Turell L]] | ||
Revision as of 10:21, 12 March 2025
Human glutathione transferase M1-1 in complex with the adduct between glutathione and nitrooleic acid
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