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| | ==Pteridine Reductase 1 (PTR1) from Trypanosoma Brucei in complex with NADP and DDD00066641== | | ==Pteridine Reductase 1 (PTR1) from Trypanosoma Brucei in complex with NADP and DDD00066641== |
| - | <StructureSection load='2vz0' size='340' side='right' caption='[[2vz0]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='2vz0' size='340' side='right'caption='[[2vz0]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2vz0]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Trybb Trybb]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VZ0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2VZ0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2vz0]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Trypanosoma_brucei_brucei Trypanosoma brucei brucei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VZ0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VZ0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=D64:6-(4-METHYLPHENYL)QUINAZOLINE-2,4-DIAMINE'>D64</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</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]] 1.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2c7v|2c7v]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D64:6-(4-METHYLPHENYL)QUINAZOLINE-2,4-DIAMINE'>D64</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Pteridine_reductase Pteridine reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.5.1.33 1.5.1.33] </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=2vz0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vz0 OCA], [https://pdbe.org/2vz0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vz0 RCSB], [https://www.ebi.ac.uk/pdbsum/2vz0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vz0 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2vz0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vz0 OCA], [http://pdbe.org/2vz0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2vz0 RCSB], [http://www.ebi.ac.uk/pdbsum/2vz0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2vz0 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/O76290_TRYBB O76290_TRYBB] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Pteridine reductase]] | + | [[Category: Large Structures]] |
| - | [[Category: Trybb]] | + | [[Category: Trypanosoma brucei brucei]] |
| - | [[Category: Fairlamb, A H]] | + | [[Category: Fairlamb AH]] |
| - | [[Category: Robinson, D A]] | + | [[Category: Robinson DA]] |
| - | [[Category: Sienkiewicz, N]] | + | [[Category: Sienkiewicz N]] |
| - | [[Category: Thompson, S]] | + | [[Category: Thompson S]] |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Short-chain dehydrogenase/reductase]]
| + | |
| - | [[Category: Trypanosomatid]]
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| Structural highlights
Function
O76290_TRYBB
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
Activity of the pterin- and folate-salvaging enzymes pteridine reductase 1 (PTR1) and dihydrofolate reductase-thymidylate synthetase (DHFR-TS) is commonly measured as a decrease in absorbance at 340 nm, corresponding to oxidation of nicotinamide adenine dinucleotide phosphate (NADPH). Although this assay has been adequate to study the biology of these enzymes, it is not amenable to support any degree of routine inhibitor assessment because its restricted linearity is incompatible with enhanced throughput microtiter plate screening. In this article, we report the development and validation of a nonenzymatically coupled screening assay in which the product of the enzymatic reaction reduces cytochrome c, causing an increase in absorbance at 550 nm. We demonstrate this assay to be robust and accurate, and we describe its utility in supporting a structure-based design, small-molecule inhibitor campaign against Trypanosoma brucei PTR1 and DHFR-TS.
Development and validation of a cytochrome c-coupled assay for pteridine reductase 1 and dihydrofolate reductase.,Shanks EJ, Ong HB, Robinson DA, Thompson S, Sienkiewicz N, Fairlamb AH, Frearson JA Anal Biochem. 2010 Jan 15;396(2):194-203. Epub 2009 Sep 11. PMID:19748480[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Shanks EJ, Ong HB, Robinson DA, Thompson S, Sienkiewicz N, Fairlamb AH, Frearson JA. Development and validation of a cytochrome c-coupled assay for pteridine reductase 1 and dihydrofolate reductase. Anal Biochem. 2010 Jan 15;396(2):194-203. Epub 2009 Sep 11. PMID:19748480 doi:10.1016/j.ab.2009.09.003
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