2wba
From Proteopedia
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| - | [[Image:2wba.png|left|200px]] | ||
| - | + | ==Properties of Trypanothione Reductase From T. brucei== | |
| + | <StructureSection load='2wba' size='340' side='right'caption='[[2wba]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2wba]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei Trypanosoma brucei brucei]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2ve2 2ve2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WBA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WBA 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]] 2.3Å</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</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=2wba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wba OCA], [https://pdbe.org/2wba PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wba RCSB], [https://www.ebi.ac.uk/pdbsum/2wba PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wba ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/TYTR_TRYBB TYTR_TRYBB] Trypanothione is the parasite analog of glutathione; this enzyme is the equivalent of glutathione reductase. | ||
| + | == 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/wb/2wba_consurf.spt"</scriptWhenChecked> | ||
| + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2wba ConSurf]. | ||
| + | <div style="clear:both"></div> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | As part of a drug discovery programme to discover new treatments for human African trypanosomiasis, recombinant trypanothione reductase from Trypanosoma brucei has been expressed, purified and characterized. The crystal structure was solved by molecular replacement to a resolution of 2.3A and found to be nearly identical to the T. cruzi enzyme (root mean square deviation 0.6A over 482 Calpha atoms). Kinetically, the K(m) for trypanothione disulphide for the T. brucei enzyme was 4.4-fold lower than for T. cruzi measured by either direct (NADPH oxidation) or DTNB-coupled assay. The K(m) for NADPH for the T. brucei enzyme was found to be 0.77microM using an NADPH-regenerating system coupled to reduction of DTNB. Both enzymes were assayed for inhibition at their respective S=K(m) values for trypanothione disulphide using a range of chemotypes, including CNS-active drugs such as clomipramine, trifluoperazine, thioridazine and citalopram. The relative IC(50) values for the two enzymes were found to vary by no more than 3-fold. Thus trypanothione reductases from these species are highly similar in all aspects, indicating that they may be used interchangeably for structure-based inhibitor design and high-throughput screening. | ||
| - | + | Comparative structural, kinetic and inhibitor studies of Trypanosoma brucei trypanothione reductase with T. cruzi.,Jones DC, Ariza A, Chow WH, Oza SL, Fairlamb AH Mol Biochem Parasitol. 2010 Jan;169(1):12-9. Epub 2009 Sep 10. PMID:19747949<ref>PMID:19747949</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 2wba" style="background-color:#fffaf0;"></div> | |
| - | + | ||
==See Also== | ==See Also== | ||
*[[Trypanothione reductase|Trypanothione reductase]] | *[[Trypanothione reductase|Trypanothione reductase]] | ||
| - | + | == References == | |
| - | == | + | <references/> |
| - | < | + | __TOC__ |
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Trypanosoma brucei brucei]] | [[Category: Trypanosoma brucei brucei]] | ||
| - | + | [[Category: Ariza A]] | |
| - | [[Category: Ariza | + | [[Category: Chow WHA]] |
| - | [[Category: Chow | + | [[Category: Fairlamb AH]] |
| - | [[Category: Fairlamb | + | [[Category: Jones D]] |
| - | [[Category: Jones | + | [[Category: Oza SL]] |
| - | [[Category: Oza | + | |
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Current revision
Properties of Trypanothione Reductase From T. brucei
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