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| | <StructureSection load='2wba' size='340' side='right'caption='[[2wba]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='2wba' size='340' side='right'caption='[[2wba]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2wba]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Trybb Trybb]. 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 [http://proteopedia.org/fgij/fg.htm?mol=2WBA FirstGlance]. <br> | + | <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='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> | + | </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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Trypanothione-disulfide_reductase Trypanothione-disulfide reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.8.1.12 1.8.1.12] </span></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'>[http://proteopedia.org/fgij/fg.htm?mol=2wba FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wba OCA], [http://pdbe.org/2wba PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wba RCSB], [http://www.ebi.ac.uk/pdbsum/2wba PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wba ProSAT]</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=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> | | </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 == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Trybb]] | + | [[Category: Trypanosoma brucei brucei]] |
| - | [[Category: Trypanothione-disulfide reductase]]
| + | [[Category: Ariza A]] |
| - | [[Category: Ariza, A]] | + | [[Category: Chow WHA]] |
| - | [[Category: Chow, W H.A]] | + | [[Category: Fairlamb AH]] |
| - | [[Category: Fairlamb, A H]] | + | [[Category: Jones D]] |
| - | [[Category: Jones, D]] | + | [[Category: Oza SL]] |
| - | [[Category: Oza, S L]] | + | |
| - | [[Category: Flavoprotein]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Redox-active center]]
| + | |
| - | [[Category: Trypnothione metabolism oxidoreductase]]
| + | |
| Structural highlights
2wba is a 2 chain structure with sequence from Trypanosoma brucei brucei. This structure supersedes the now removed PDB entry 2ve2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 2.3Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
TYTR_TRYBB Trypanothione is the parasite analog of glutathione; this enzyme is the equivalent of glutathione reductase.
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 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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jones DC, Ariza A, Chow WH, Oza SL, Fairlamb AH. Comparative structural, kinetic and inhibitor studies of Trypanosoma brucei trypanothione reductase with T. cruzi. Mol Biochem Parasitol. 2010 Jan;169(1):12-9. Epub 2009 Sep 10. PMID:19747949 doi:10.1016/j.molbiopara.2009.09.002
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