3jqa: Difference between revisions
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<StructureSection load='3jqa' size='340' side='right' caption='[[3jqa]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='3jqa' size='340' side='right' caption='[[3jqa]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3jqa]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3jqa]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Trypanosoma_(trypanozoon)_brucei Trypanosoma (trypanozoon) brucei]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3bmg 3bmg]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JQA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JQA FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DX4:2-AMINO-1,9-DIHYDRO-6H-PURINE-6-THIONE'>DX4</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DX4:2-AMINO-1,9-DIHYDRO-6H-PURINE-6-THIONE'>DX4</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene></td></tr> | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSX:S-OXY+CYSTEINE'>CSX</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3jq6|3jq6]], [[3jq7|3jq7]], [[3jq8|3jq8]], [[3jq9|3jq9]], [[3jqb|3jqb]], [[3jqc|3jqc]], [[3jqd|3jqd]], [[3jqe|3jqe]], [[3jqf|3jqf]], [[3jqg|3jqg]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3jq6|3jq6]], [[3jq7|3jq7]], [[3jq8|3jq8]], [[3jq9|3jq9]], [[3jqb|3jqb]], [[3jqc|3jqc]], [[3jqd|3jqd]], [[3jqe|3jqe]], [[3jqf|3jqf]], [[3jqg|3jqg]]</td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTR1, Tb927.8.2210 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5691 Trypanosoma brucei])</td></tr> | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTR1, Tb927.8.2210 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=5691 Trypanosoma (Trypanozoon) brucei])</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='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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3jqa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jqa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3jqa RCSB], [http://www.ebi.ac.uk/pdbsum/3jqa PDBsum]</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=3jqa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jqa OCA], [http://pdbe.org/3jqa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jqa RCSB], [http://www.ebi.ac.uk/pdbsum/3jqa PDBsum]</span></td></tr> | ||
</table> | </table> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
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<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </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/ | </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=3jqa ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 3jqa" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Pteridine reductase]] | [[Category: Pteridine reductase]] | ||
[[Category: Hunter, W N]] | [[Category: Hunter, W N]] | ||
[[Category: Tulloch, L B]] | [[Category: Tulloch, L B]] | ||
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[[Category: Ptr1]] | [[Category: Ptr1]] | ||
[[Category: Short chain dehydrogenase]] | [[Category: Short chain dehydrogenase]] | ||
[[Category: Trypanosoma brucei]] | |||
Revision as of 23:11, 7 February 2016
Crystal structure of pteridine reductase 1 (PTR1) from Trypanosoma brucei in ternary complex with cofactor (NADP+) and inhibitor 2-amino-1,9-dihydro-6H-purine-6-thione (DX4)Crystal structure of pteridine reductase 1 (PTR1) from Trypanosoma brucei in ternary complex with cofactor (NADP+) and inhibitor 2-amino-1,9-dihydro-6H-purine-6-thione (DX4)
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 PubMedPteridine reductase (PTR1) is a target for drug development against Trypanosoma and Leishmania species, parasites that cause serious tropical diseases and for which therapies are inadequate. We adopted a structure-based approach to the design of novel PTR1 inhibitors based on three molecular scaffolds. A series of compounds, most newly synthesized, were identified as inhibitors with PTR1-species specific properties explained by structural differences between the T. brucei and L. major enzymes. The most potent inhibitors target T. brucei PTR1, and two compounds displayed antiparasite activity against the bloodstream form of the parasite. PTR1 contributes to antifolate drug resistance by providing a molecular bypass of dihydrofolate reductase (DHFR) inhibition. Therefore, combining PTR1 and DHFR inhibitors might improve therapeutic efficacy. We tested two new compounds with known DHFR inhibitors. A synergistic effect was observed for one particular combination highlighting the potential of such an approach for treatment of African sleeping sickness. Structure-Based Design of Pteridine Reductase Inhibitors Targeting African Sleeping Sickness and the Leishmaniases.,Tulloch LB, Martini VP, Iulek J, Huggan JK, Lee JH, Gibson CL, Smith TK, Suckling CJ, Hunter WN J Med Chem. 2009 Nov 16. PMID:19916554[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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