6how
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Trypanosoma brucei PTR1 in complex with the triazine inhibitor 2a (F219).== | |
| + | <StructureSection load='6how' size='340' side='right'caption='[[6how]], [[Resolution|resolution]] 1.92Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6how]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6HOW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6HOW FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GJQ:(2~{R})-1-(3,4-dichlorophenyl)-2-(4-nitrophenyl)-2~{H}-1,3,5-triazine-4,6-diamine'>GJQ</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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6hnc|6hnc]], [[6hnr|6hnr]]</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=6how FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6how OCA], [http://pdbe.org/6how PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6how RCSB], [http://www.ebi.ac.uk/pdbsum/6how PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6how ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Cycloguanil is a known dihydrofolate-reductase (DHFR) inhibitor, but there is no evidence of its activity on pteridine reductase (PTR), the main metabolic bypass to DHFR inhibition in trypanosomatid parasites. Here, we provide experimental evidence of cycloguanil as an inhibitor of Trypanosoma brucei PTR1 ( TbPTR1). A small library of cycloguanil derivatives was developed, resulting in 1 and 2a having IC50 values of 692 and 186 nM, respectively, toward TbPTR1. Structural analysis revealed that the increased potency of 1 and 2a is due to the combined contributions of hydrophobic interactions, H-bonds, and halogen bonds. Moreover, in vitro cell-growth-inhibition tests indicated that 2a is also effective on T. brucei. The simultaneous inhibition of DHFR and PTR1 activity in T. brucei is a promising new strategy for the treatment of human African trypanosomiasis. For this purpose, 1,6-dihydrotriazines represent new molecular tools to develop potent dual PTR and DHFR inhibitors. | ||
| - | + | Structural Insights into the Development of Cycloguanil Derivatives as Trypanosoma brucei Pteridine-Reductase-1 Inhibitors.,Landi G, Linciano P, Borsari C, Bertolacini CP, Moraes CB, Cordeiro-da-Silva A, Gul S, Witt G, Kuzikov M, Costi MP, Pozzi C, Mangani S ACS Infect Dis. 2019 May 1. doi: 10.1021/acsinfecdis.8b00358. PMID:31012301<ref>PMID:31012301</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6how" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
[[Category: Landi, G]] | [[Category: Landi, G]] | ||
[[Category: Mangani, S]] | [[Category: Mangani, S]] | ||
[[Category: Pozzi, C]] | [[Category: Pozzi, C]] | ||
| + | [[Category: Oxidoreductase]] | ||
| + | [[Category: Pteridine reductase]] | ||
| + | [[Category: Ptr1]] | ||
| + | [[Category: Tbptr1]] | ||
| + | [[Category: Triazine inhibitor]] | ||
| + | [[Category: Trypanosoma brucei]] | ||
Revision as of 11:18, 10 May 2019
Trypanosoma brucei PTR1 in complex with the triazine inhibitor 2a (F219).
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