4cmi: Difference between revisions
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<StructureSection load='4cmi' size='340' side='right' caption='[[4cmi]], [[Resolution|resolution]] 1.90Å' scene=''> | <StructureSection load='4cmi' size='340' side='right' caption='[[4cmi]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4cmi]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CMI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CMI FirstGlance]. <br> | <table><tr><td colspan='2'>[[4cmi]] 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=4CMI OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CMI FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=M4V:2-AMINO-6-(4-BROMOPHENYL)-5-PHENYL-3H-PYRROLO[2,3-D]PYRIMIDIN-4(7H)-ONE'>M4V</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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=M4V:2-AMINO-6-(4-BROMOPHENYL)-5-PHENYL-3H-PYRROLO[2,3-D]PYRIMIDIN-4(7H)-ONE'>M4V</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> | ||
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</div> | </div> | ||
<div class="pdbe-citations 4cmi" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4cmi" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Pteridine reductase]] | [[Category: Pteridine reductase]] | ||
[[Category: Trybb]] | |||
[[Category: Barrack, K L]] | [[Category: Barrack, K L]] | ||
[[Category: Hunter, W N]] | [[Category: Hunter, W N]] | ||
[[Category: Oxidoreductase]] | [[Category: Oxidoreductase]] | ||
[[Category: Short-chain dehydrogenase/reductase]] | [[Category: Short-chain dehydrogenase/reductase]] | ||
Revision as of 10:49, 16 November 2017
Crystal structure of pteridine reductase 1 (PTR1) from Trypanosoma brucei in ternary complex with cofactor and inhibitorCrystal structure of pteridine reductase 1 (PTR1) from Trypanosoma brucei in ternary complex with cofactor and inhibitor
Structural highlights
Publication Abstract from PubMedThe treatment of Human African trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important; pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp., has been identified as a candidate target, and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 from Trypanosoma brucei (J. Med. Chem. 2010, 53, 221-229). In this study, 61 new pyrrolo[2,3-d]pyrimidines have been prepared, designed with input from new crystal structures of 23 of these compounds complexed with PTR1, and evaluated in screens for enzyme inhibitory activity against PTR1 and in vitro antitrypanosomal activity. Eight compounds were sufficiently active in both screens to take forward to in vivo evaluation. Thus, although evidence for trypanocidal activity in a stage I disease model in mice was obtained, the compounds were too toxic to mice for further development. Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1.,Khalaf AI, Huggan JK, Suckling CJ, Gibson CL, Stewart K, Giordani F, Barrett MP, Wong PE, Barrack KL, Hunter WN J Med Chem. 2014 Aug 14;57(15):6479-94. doi: 10.1021/jm500483b. Epub 2014 Jul 29. PMID:25007262[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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