1bwc

From Proteopedia

(Difference between revisions)

Current revision

STRUCTURE OF HUMAN GLUTATHIONE REDUCTASE COMPLEXED with AJOENE INHIBITOR AND SUBVERSIVE SUBSTRATE

Structural highlights

1bwc is a 1 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 2.1Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GSHR_HUMAN Maintains high levels of reduced glutathione in the cytosol.

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

Ajoene ((E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide), a garlic-derived natural compound, is a covalent inhibitor as well as a substrate of human glutathione reductase (GR) and Trypanosoma cruzi trypanothione reductase (TR). The 2.1-A resolution crystal structure of GR inhibited by (E)-ajoene revealed a mixed disulfide between the active site Cys58 and the CH2=CH-CH2-SO-CH2-CH=CH-S moiety of ajoene. The modified enzyme has a markedly increased oxidase activity when compared to free GR. GR reduces (Z)-ajoene with a kcat/Km of 6.8 x 10(3) M-1 s-1 yielding 4,5,9-trithiadodeca-1, 6,11-triene (deoxyajoene) and 4,8,9,13-tetrathiahexadeca-1,6,10, 15-tetraene as stable reaction products. The reaction leads also to the formation of single-electron reduced products and concomitantly superoxide anion radicals as shown by coupling the reaction to the reduction of cytochrome c. The interactions between the flavoenzymes and ajoene are expected to increase the oxidative stress of the respective cell. The antiparasitic and cytostatic actions of ajoene may at least in part be due to the multiple effects on key enzymes of the antioxidant thiol metabolism.

Ajoene is an inhibitor and subversive substrate of human glutathione reductase and Trypanosoma cruzi trypanothione reductase: crystallographic, kinetic, and spectroscopic studies.,Gallwitz H, Bonse S, Martinez-Cruz A, Schlichting I, Schumacher K, Krauth-Siegel RL J Med Chem. 1999 Feb 11;42(3):364-72. PMID:9986706^[1]

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

References

↑ Gallwitz H, Bonse S, Martinez-Cruz A, Schlichting I, Schumacher K, Krauth-Siegel RL. Ajoene is an inhibitor and subversive substrate of human glutathione reductase and Trypanosoma cruzi trypanothione reductase: crystallographic, kinetic, and spectroscopic studies. J Med Chem. 1999 Feb 11;42(3):364-72. PMID:9986706 doi:10.1021/jm980471k

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/1bwc"

@@ Line 3: / Line 3: @@
 <StructureSection load='1bwc' size='340' side='right'caption='[[1bwc]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1bwc]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1BWC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1BWC FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1bwc]] is a 1 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=1BWC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1BWC FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AJ3:3-(PROP-2-ENE-1-SULFINYL)-PROPENE-1-THIOL'>AJ3</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</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]] 2.1&#8491;</td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Glutathione-disulfide_reductase Glutathione-disulfide reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.7 1.8.1.7] </span></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AJ3:3-(PROP-2-ENE-1-SULFINYL)-PROPENE-1-THIOL'>AJ3</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene></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=1bwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bwc OCA], [http://pdbe.org/1bwc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1bwc RCSB], [http://www.ebi.ac.uk/pdbsum/1bwc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1bwc ProSAT]</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=1bwc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1bwc OCA], [https://pdbe.org/1bwc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1bwc RCSB], [https://www.ebi.ac.uk/pdbsum/1bwc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1bwc ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/GSHR_HUMAN GSHR_HUMAN]] Maintains high levels of reduced glutathione in the cytosol.
+[https://www.uniprot.org/uniprot/GSHR_HUMAN GSHR_HUMAN] Maintains high levels of reduced glutathione in the cytosol.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 15: / Line 15: @@
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bw/1bwc_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
@@ Line 36: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Glutathione-disulfide reductase]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Bonse, S]]
+[[Category: Bonse S]]
-[[Category: Gallwitz, H]]
+[[Category: Gallwitz H]]
-[[Category: Krauth-Siegel, R L]]
+[[Category: Krauth-Siegel RL]]
-[[Category: Martinez-Cruz, A]]
+[[Category: Martinez-Cruz A]]
-[[Category: Schlichting, I]]
+[[Category: Schlichting I]]
-[[Category: Schumacher, K]]
+[[Category: Schumacher K]]
-[[Category: Flavoenzyme]]
-[[Category: Oxidoreductase]]
-[[Category: Redox-active center]]

1bwc

From Proteopedia

Current revision

STRUCTURE OF HUMAN GLUTATHIONE REDUCTASE COMPLEXED with AJOENE INHIBITOR AND SUBVERSIVE SUBSTRATE

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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