2x99: Difference between revisions
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==Thioredoxin glutathione reductase from Schistosoma mansoni in complex with NADPH== | ==Thioredoxin glutathione reductase from Schistosoma mansoni in complex with NADPH== | ||
<StructureSection load='2x99' size='340' side='right' caption='[[2x99]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='2x99' size='340' side='right'caption='[[2x99]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2x99]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Blood_fluke Blood fluke]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X99 OCA]. For a <b>guided tour on the structure components</b> use [http:// | <table><tr><td colspan='2'>[[2x99]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Blood_fluke Blood fluke]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X99 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2X99 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GSH:GLUTATHIONE'>GSH</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2x8h|2x8h]], [[2x8g|2x8g]], [[2v6o|2v6o]], [[2x8c|2x8c]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2x8h|2x8h]], [[2x8g|2x8g]], [[2v6o|2v6o]], [[2x8c|2x8c]]</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thioredoxin-disulfide_reductase Thioredoxin-disulfide reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.9 1.8.1.9] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thioredoxin-disulfide_reductase Thioredoxin-disulfide reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.9 1.8.1.9] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2x99 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x99 OCA], [http://pdbe.org/2x99 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2x99 RCSB], [http://www.ebi.ac.uk/pdbsum/2x99 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2x99 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Blood fluke]] | [[Category: Blood fluke]] | ||
[[Category: Large Structures]] | |||
[[Category: Thioredoxin-disulfide reductase]] | [[Category: Thioredoxin-disulfide reductase]] | ||
[[Category: Angelucci, F]] | [[Category: Angelucci, F]] | ||
Revision as of 18:07, 8 July 2020
Thioredoxin glutathione reductase from Schistosoma mansoni in complex with NADPHThioredoxin glutathione reductase from Schistosoma mansoni in complex with NADPH
Structural highlights
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 PubMedSchistosomiasis is the second most widespread human parasitic disease. It is principally treated with one drug, praziquantel that is administered to 100 million people each year; less sensitive strains of schistosomes are emerging. One of the most appealing drug targets against schistosomiasis is thioredoxin glutathione reductase (TGR). This natural chimeric enzyme is a peculiar fusion of a glutaredoxin domain with a thioredoxin Selenocysteine (Sec)-containing reductase domain. Sec is located on a flexible C-terminal arm that is usually disordered in the available structures of the protein and is essential for the full catalytic activity of TGR. In this study, we dissect the catalytic cycle of Schistosoma mansoni TGR (SmTGR) by structural and functional analysis of Sec597Cys mutant. The crystallographic data presented herein include: the oxidized form (at 1.9 A resolution); the NADPH- and GSH-bound forms (2.3 A and 1.9 A , respectively); and a different crystal form of the (partially) reduced enzyme (3.1 A ), showing the physiological dimer and the entire C-terminus of one subunit. Whenever possible, we determined the rate constants for the interconversion between the different oxidation states of TGR by kinetic methods. By combining the crystallographic analysis with computer modelling, we were able to throw further light on the mechanism of action of S. mansoni TGR. In particular, we propose hereby the putative functionally relevant conformational change of the C-terminus after the transfer of reducing equivalents from NADPH to the redox sites of the enzyme. Mapping the catalytic cycle of Schistosoma mansoni thioredoxin glutathione reductase by x-ray crystallography.,Angelucci F, Dimastrogiovanni D, Boumis G, Brunori M, Miele AE, Saccoccia F, Bellelli A J Biol Chem. 2010 Jul 21. PMID:20659890[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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