2x8c: Difference between revisions
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< | ==Thioredoxin glutathione reductase from Schistosoma mansoni with the reduced C-terminal end== | ||
<StructureSection load='2x8c' size='340' side='right'caption='[[2x8c]], [[Resolution|resolution]] 3.10Å' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2x8c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Schistosoma_mansoni Schistosoma mansoni]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X8C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X8C 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]] 3.1Å</td></tr> | |||
- | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</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=2x8c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x8c OCA], [https://pdbe.org/2x8c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x8c RCSB], [https://www.ebi.ac.uk/pdbsum/2x8c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x8c ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q962Y6_SCHMA Q962Y6_SCHMA] | |||
== 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/x8/2x8c_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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/main_output.php?pdb_ID=2x8c ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Schistosomiasis 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<ref>PMID:20659890</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2x8c" style="background-color:#fffaf0;"></div> | |||
== | ==See Also== | ||
*[[Thioredoxin Glutathione Reductase|Thioredoxin Glutathione Reductase]] | |||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Schistosoma mansoni]] | [[Category: Schistosoma mansoni]] | ||
[[Category: Angelucci F]] | |||
[[Category: Angelucci | [[Category: Bellelli A]] | ||
[[Category: Bellelli | [[Category: Boumis G]] | ||
[[Category: Boumis | [[Category: Brunori M]] | ||
[[Category: Brunori | [[Category: Dimastrogiovanni D]] | ||
[[Category: Dimastrogiovanni | [[Category: Miele AE]] | ||
[[Category: Miele | [[Category: Saccoccia F]] | ||
[[Category: Saccoccia | |||
Latest revision as of 11:04, 23 October 2024
Thioredoxin glutathione reductase from Schistosoma mansoni with the reduced C-terminal endThioredoxin glutathione reductase from Schistosoma mansoni with the reduced C-terminal end
Structural highlights
FunctionEvolutionary 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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