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2r3x

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Crystal structure of an R15L hGSTA1-1 mutant complexed with S-hexyl-glutathione

Structural highlights

2r3x 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 1.8Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GSTA1_HUMAN Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.^[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Arg15, conserved in class Alpha GSTs (glutathione transferases), is located at the interface between the G- and H-sites of the active site where its cationic guanidinium group might play a role in catalysis and ligand binding. Arg15 in human GSTA1-1 was replaced with a leucine and crystallographic, spectroscopic, thermodynamic and molecular docking methods were used to investigate the contribution made by Arg15 towards (i) the binding of glutathione (GSH) to the G-site, (ii) the pK(a) of the thiol group of GSH, (iii) the stabilization of an analog of the anionic transition state of the S(N)Ar reaction between 1-chloro-2,4-dinitrobenzene (CDNB) and GSH, and, (iv) the binding of the anionic non-substrate ligand 8-anilino-1-naphthalene sulphonate (ANS) to the H-site. While the R15L mutation substantially diminishes the CDNB-GSH conjugating activity of the enzyme, it has little effect on protein structure and stability. Arg15 does not contribute significantly towards the enzyme's affinity for GSH but does determine the reactivity of GSH by reducing the thiol's pK(a) from 7.6 to 6.6. The anionic sigma-complex formed between GSH and 1,3,5-trinitrobenzene is stabilized by Arg15, suggesting that it also stabilizes the transition state formed in the S(N)Ar reaction between GSH and CDNB. The trinitrocyclohexadienate moiety of the sigma-complex binds the H-site where the catalytic residue, Tyr9, was identified to hydrogen bond to an o-nitro group of the sigma-complex. The affinity for ANS at the H-site is decreased about 3-fold by the R15L mutation implicating the positive electrostatic potential of Arg15 in securing the organic anion at this site.

Arginine 15 stabilizes an S(N)Ar reaction transition state and the binding of anionic ligands at the active site of human glutathione transferase A1-1.,Gildenhuys S, Dobreva M, Kinsley N, Sayed Y, Burke J, Pelly S, Gordon GP, Sayed M, Sewell T, Dirr HW Biophys Chem. 2010 Feb;146(2-3):118-25. Epub 2009 Nov 18. PMID:19959275^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Achilonu I, Gildenhuys S, Fisher L, Burke J, Fanucchi S, Sewell BT, Fernandes M, Dirr HW. The role of a topologically conserved isoleucine in glutathione transferase structure, stability and function. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Jul 1;66(Pt, 7):776-80. Epub 2010 Jun 23. PMID:20606271 doi:10.1107/S1744309110019135
↑ Gildenhuys S, Dobreva M, Kinsley N, Sayed Y, Burke J, Pelly S, Gordon GP, Sayed M, Sewell T, Dirr HW. Arginine 15 stabilizes an S(N)Ar reaction transition state and the binding of anionic ligands at the active site of human glutathione transferase A1-1. Biophys Chem. 2010 Feb;146(2-3):118-25. Epub 2009 Nov 18. PMID:19959275 doi:10.1016/j.bpc.2009.11.003

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2r3x"

@@ Line 1: / Line 1: @@
 ==Crystal structure of an R15L hGSTA1-1 mutant complexed with S-hexyl-glutathione==
-<StructureSection load='2r3x' size='340' side='right' caption='[[2r3x]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
+<StructureSection load='2r3x' size='340' side='right'caption='[[2r3x]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2r3x]] 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=2R3X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2R3X FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2r3x]] 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=2R3X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2R3X FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GTX:S-HEXYLGLUTATHIONE'>GTX</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]] 1.8&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GSTA1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTX:S-HEXYLGLUTATHIONE'>GTX</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=2r3x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r3x OCA], [https://pdbe.org/2r3x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2r3x RCSB], [https://www.ebi.ac.uk/pdbsum/2r3x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2r3x ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2r3x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2r3x OCA], [http://pdbe.org/2r3x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2r3x RCSB], [http://www.ebi.ac.uk/pdbsum/2r3x PDBsum]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/GSTA1_HUMAN GSTA1_HUMAN]] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.<ref>PMID:20606271</ref>
+[https://www.uniprot.org/uniprot/GSTA1_HUMAN GSTA1_HUMAN] Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.<ref>PMID:20606271</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/r3/2r3x_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/r3/2r3x_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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=2r3x ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 31: / Line 31: @@
 ==See Also==
-*[[Glutathione S-transferase|Glutathione S-transferase]]
+*[[Glutathione S-transferase 3D structures|Glutathione S-transferase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Glutathione transferase]]
+[[Category: Homo sapiens]]
-[[Category: Human]]
+[[Category: Large Structures]]
-[[Category: Burke, J P.W G]]
+[[Category: Burke JPWG]]
-[[Category: Dirr, H W]]
+[[Category: Dirr HW]]
-[[Category: Kinsley, N]]
+[[Category: Kinsley N]]
-[[Category: Sayed, M]]
+[[Category: Sayed M]]
-[[Category: Sewell, T]]
+[[Category: Sewell T]]
-[[Category: Human alpha class glutathione transferase 1-1]]
-[[Category: S-hexyl glutathione]]
-[[Category: Transferase]]
-[[Category: X-ray crystal structure]]

2r3x

From Proteopedia

Current revision

Crystal structure of an R15L hGSTA1-1 mutant complexed with S-hexyl-glutathione

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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