3sqp: Difference between revisions
No edit summary |
No edit summary |
||
| (6 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
==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=''> | |||
== Structural highlights == | |||
<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='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='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'>[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> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/GSHR_HUMAN GSHR_HUMAN] Maintains high levels of reduced glutathione in the cytosol. | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:21888766</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3sqp" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Glutathione Reductase|Glutathione Reductase]] | *[[Glutathione Reductase|Glutathione Reductase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Fritz-Wolf | [[Category: Large Structures]] | ||
[[Category: Goebel | [[Category: Fritz-Wolf K]] | ||
[[Category: Koenig | [[Category: Goebel U]] | ||
[[Category: Schirmer | [[Category: Koenig I]] | ||
[[Category: Schirmer RH]] | |||