6hnc
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6hnc is ON HOLD until Paper Publication Authors: Landi, G., Pozzi, C., Mangani, S. Description: Trypanosoma brucei PTR1 in complex with cycloguanil...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Trypanosoma brucei PTR1 in complex with cycloguanil== | |
| + | <StructureSection load='6hnc' size='340' side='right'caption='[[6hnc]], [[Resolution|resolution]] 1.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6hnc]] 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=6HNC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6HNC FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1CY:1-(4-CHLOROPHENYL)-6,6-DIMETHYL-1,6-DIHYDRO-1,3,5-TRIAZINE-2,4-DIAMINE'>1CY</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></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=6hnc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6hnc OCA], [https://pdbe.org/6hnc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6hnc RCSB], [https://www.ebi.ac.uk/pdbsum/6hnc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6hnc ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/O76290_TRYBB O76290_TRYBB] | ||
| + | <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> |
| - | [[Category: Landi | + | <div class="pdbe-citations 6hnc" style="background-color:#fffaf0;"></div> |
| - | [[Category: Mangani | + | |
| - | [[Category: Pozzi | + | ==See Also== |
| + | *[[Pteridine reductase|Pteridine reductase]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Trypanosoma brucei brucei]] | ||
| + | [[Category: Landi G]] | ||
| + | [[Category: Mangani S]] | ||
| + | [[Category: Pozzi C]] | ||
Current revision
Trypanosoma brucei PTR1 in complex with cycloguanil
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