5k6a: Difference between revisions
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==Trypanosoma brucei Pteridine reductase 1 (PTR1) in complex with compound 1== | |||
<StructureSection load='5k6a' size='340' side='right' caption='[[5k6a]], [[Resolution|resolution]] 1.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5k6a]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5K6A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5K6A FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=6QT:(2~{R})-2-(3-HYDROXYPHENYL)-6-OXIDANYL-2,3-DIHYDROCHROMEN-4-ONE'>6QT</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</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>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene></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=5k6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5k6a OCA], [http://pdbe.org/5k6a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5k6a RCSB], [http://www.ebi.ac.uk/pdbsum/5k6a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5k6a ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Flavonoids have previously been identified as antiparasitic agents and pteridine reductase 1 (PTR1) inhibitors. Herein, we focus our attention on the chroman-4-one scaffold. Three chroman-4-one analogues (1-3) of previously published chromen-4-one derivatives were synthesized and biologically evaluated against parasitic enzymes (Trypanosoma brucei PTR1-TbPTR1 and Leishmania major-LmPTR1) and parasites (Trypanosoma brucei and Leishmania infantum). A crystal structure of TbPTR1 in complex with compound 1 and the first crystal structures of LmPTR1-flavanone complexes (compounds 1 and 3) were solved. The inhibitory activity of the chroman-4-one and chromen-4-one derivatives was explained by comparison of observed and predicted binding modes of the compounds. Compound 1 showed activity both against the targeted enzymes and the parasites with a selectivity index greater than 7 and a low toxicity. Our results provide a basis for further scaffold optimization and structure-based drug design aimed at the identification of potent anti-trypanosomatidic compounds targeting multiple PTR1 variants. | |||
Chroman-4-One Derivatives Targeting Pteridine Reductase 1 and Showing Anti-Parasitic Activity.,Di Pisa F, Landi G, Dello Iacono L, Pozzi C, Borsari C, Ferrari S, Santucci M, Santarem N, Cordeiro-da-Silva A, Moraes CB, Alcantara LM, Fontana V, Freitas-Junior LH, Gul S, Kuzikov M, Behrens B, Pohner I, Wade RC, Costi MP, Mangani S Molecules. 2017 Mar 8;22(3). pii: E426. doi: 10.3390/molecules22030426. PMID:28282886<ref>PMID:28282886</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5k6a" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Landi, G]] | [[Category: Landi, G]] | ||
[[Category: Mangani, S]] | [[Category: Mangani, S]] | ||
[[Category: | [[Category: Pisa, F Di]] | ||
[[Category: Pozzi, C]] | [[Category: Pozzi, C]] | ||
[[Category: Lacono, L Dello]] | |||
[[Category: Oxidoreductase]] | |||
[[Category: Pteridine reductase]] | |||
[[Category: Trypanosoma brucei]] | |||