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| | ==Structure of human glutathione reductase complexed with pyocyanin, an agent with antimalarial activity== | | ==Structure of human glutathione reductase complexed with pyocyanin, an agent with antimalarial activity== |
| - | <StructureSection load='3sqp' size='340' side='right' caption='[[3sqp]], [[Resolution|resolution]] 2.21Å' scene=''> | + | <StructureSection load='3sqp' size='340' side='right'caption='[[3sqp]], [[Resolution|resolution]] 2.21Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3sqp]] 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=3SQP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3SQP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3sqp]] 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=3SQP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SQP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3J8:5-METHYLPHENAZIN-1(5H)-ONE'>3J8</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.21Å</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=3J8:5-METHYLPHENAZIN-1(5H)-ONE'>3J8</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3sqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sqp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3sqp RCSB], [http://www.ebi.ac.uk/pdbsum/3sqp PDBsum]</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=3sqp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3sqp OCA], [https://pdbe.org/3sqp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3sqp RCSB], [https://www.ebi.ac.uk/pdbsum/3sqp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3sqp ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == 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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3sqp" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Glutathione-disulfide reductase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[Category: Fritz-Wolf, K]] | + | [[Category: Fritz-Wolf K]] |
| - | [[Category: Goebel, U]] | + | [[Category: Goebel U]] |
| - | [[Category: Koenig, I]] | + | [[Category: Koenig I]] |
| - | [[Category: Schirmer, R H]] | + | [[Category: Schirmer RH]] |
| - | [[Category: Alternative initiation]]
| + | |
| - | [[Category: Cellular reductant]]
| + | |
| - | [[Category: Flavoprotein]]
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| - | [[Category: Glutathione reductase]]
| + | |
| - | [[Category: Mitochondrion]]
| + | |
| - | [[Category: Oxidoreductase]]
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| - | [[Category: Oxidoreductase-antibiotic complex]]
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| - | [[Category: Phosphoprotein]]
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| - | [[Category: Plasmodium falciparum]]
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| - | [[Category: Pyocyanin]]
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| - | [[Category: Redox-active center]]
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| - | [[Category: Transit peptide]]
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| Structural highlights
Function
GSHR_HUMAN Maintains high levels of reduced glutathione in the cytosol.
Publication Abstract from PubMed
The quorum sensor and signalling molecule pyocyanin (PYO) contributes significantly to the pathophysiology of Pseudomonas aeruginosa infections. Comparison to phenothiazine drugs suggests that the antimalarial compound methylene blue (MB) can be regarded as a sulfur analog of PYO. This working hypothesis would explain why the synthetic drug MB behaves as a compound shaped in biological evolution. Here we report on redox-associated biological and biochemical properties of PYO in direct comparison to its synthetic analog MB. We quantitatively describe the reactivity of both compounds toward cellular reductants, the reactivity of their reduced leuco-forms towards O(2), and their interactions with FAD-containing disulfide reductases. Furthermore, the interaction of PYO with human glutathione reductase was studied in structural detail by x-ray crystallography, showing that a single PYO molecule binds to the intersubunit cavity of the enzyme. Like MB, also PYO was also found to be active against blood schizonts of the malaria parasite P. falciparum in vitro. Furthermore, both compounds were active against the disease transmitting gametocyte forms of the parasites, which was systematically studied in vitro. As shown for mice, PYO is too toxic to be used as a drug. It may, however, have antimalarial activity in numerous human patients with concomitant Pseudomonas infections. MB, in contrast to PYO, is well tolerated and represents a promising agent for MB-based combination therapies against malaria. Current and future clinical studies can be guided by the comparisons between MB and PYO reported here. Additionally, it is of interest to study if and to what extent the protection from malaria in patients with cystic fibrosis or with severe wound infections is based on PYO produced by Pseudomonas species.
The bacterial redox signaller pyocyanin as an antiplasmodial agent: comparisons with its thioanalog methylene blue.,Kasozi DM, Gromer S, Adler H, Zocher K, Rahlfs S, Wittlin S, Fritz-Wolf K, Schirmer RH, Becker K Redox Rep. 2011;16(4):154-65. PMID:21888766[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kasozi DM, Gromer S, Adler H, Zocher K, Rahlfs S, Wittlin S, Fritz-Wolf K, Schirmer RH, Becker K. The bacterial redox signaller pyocyanin as an antiplasmodial agent: comparisons with its thioanalog methylene blue. Redox Rep. 2011;16(4):154-65. PMID:21888766 doi:10.1179/174329211X13049558293678
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