3ik7: Difference between revisions
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== | ==Human glutathione transferase a4-4 with GSDHN== | ||
[[3ik7]] is a 4 chain structure with sequence from [ | <StructureSection load='3ik7' size='340' side='right'caption='[[3ik7]], [[Resolution|resolution]] 1.97Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3ik7]] 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=3IK7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IK7 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]] 1.97Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BOB:(S)-2-AMINO-5-((R)-1-(CARBOXYMETHYLAMINO)-3-((3S,4R)-1,4-DIHYDROXYNONAN-3-YLTHIO)-1-OXOPROPAN-2-YLAMINO)-5-OXOPENTANOIC+ACID'>BOB</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3ik7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ik7 OCA], [https://pdbe.org/3ik7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ik7 RCSB], [https://www.ebi.ac.uk/pdbsum/3ik7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ik7 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GSTA4_HUMAN GSTA4_HUMAN] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. This isozyme has a high catalytic efficiency with 4-hydroxyalkenals such as 4-hydroxynonenal (4-HNE).<ref>PMID:10329152</ref> <ref>PMID:20085333</ref> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ik/3ik7_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3ik7 ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Conjugation to glutathione (GSH) by glutathione transferase A4-4 (GSTA4-4) is a major route of elimination for the lipid peroxidation product 4-hydroxynonenal (HNE), a toxic compound that contributes to numerous diseases. Both enantiomers of HNE are presumed to be toxic, and GSTA4-4 has negligible stereoselectivity toward them, despite its high catalytic chemospecificity for alkenals. In contrast to the highly flexible, and substrate promiscuous, GSTA1-1 isoform that has poor catalytic efficiency with HNE, GSTA4-4 has been postulated to be a rigid template that is preorganized for HNE metabolism. However, the combination of high substrate chemoselectivity and low substrate stereoselectivity is intriguing. The mechanism by which GSTA4-4 achieves this combination is important, because it must metabolize both enantiomers of HNE to efficiently detoxify the biologically formed mixture. The crystal structures of GSTA4-4 and an engineered variant of GSTA1-1 with high catalytic efficiency toward HNE, cocrystallized with a GSH-HNE conjugate analogue, demonstrate that GSTA4-4 undergoes no enantiospecific induced fit; instead, the active site residue Arg15 is ideally located to interact with the 4-hydroxyl group of either HNE enantiomer. The results reveal an evolutionary strategy for achieving biologically useful stereopromiscuity toward a toxic racemate, concomitant with high catalytic efficiency and substrate specificity toward an endogenously formed toxin. | |||
Substrate specificity combined with stereopromiscuity in glutathione transferase A4-4-dependent metabolism of 4-hydroxynonenal.,Balogh LM, Le Trong I, Kripps KA, Shireman LM, Stenkamp RE, Zhang W, Mannervik B, Atkins WM Biochemistry. 2010 Feb 23;49(7):1541-8. PMID:20085333<ref>PMID:20085333</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3ik7" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Glutathione S-transferase|Glutathione S-transferase]] | *[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Atkins WM]] | ||
[[Category: | [[Category: Balogh LM]] | ||
[[Category: Trong | [[Category: Le Trong I]] | ||
[[Category: | [[Category: Stenkamp RE]] | ||
Latest revision as of 07:52, 6 September 2023
Human glutathione transferase a4-4 with GSDHN
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