5ebk

Trypanothione reductase in complex with 6-(sec-butoxy)-2-((3-chlorophenyl)thio)pyrimidin-4-amine

spinqualitylabelsall models 5ebk, resolution 3.51Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5ebk is a 2 chain structure with sequence from Leishmania infantum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.51Å Ligands: FAD, RDS, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A4HSF7_LEIIN Publication Abstract from PubMed The study presented here aimed at identifying a new class of compounds acting against Leishmania parasites, the causative agent of Leishmaniasis. For this purpose, the thioether derivatives of our in-house library have been evaluated in whole-cell screening assays in order to determine their in vitro activity against Leishmania protozoan. Among them, promising results have been achieved with compound RDS 777 (6-(sec-butoxy)-2-((3-chlorophenyl)thio)pyrimidin-4-amine) (IC50 = 29.43 microM), which is able to impair the mechanism of the parasite defence against the reactive oxygen species by inhibiting the trypanothione reductase (TR) with high efficiency (Ki 0.25 +/- 0.18 microM). The X-ray structure of L. infantum TR in complex with RDS 777 disclosed the mechanism of action of this compound that binds to the catalytic site and engages in hydrogen bonds the residues more involved in the catalysis, namely Glu466', Cys57 and Cys52, thereby inhibiting the trypanothione binding and avoiding its reduction. Inhibition of Leishmania infantum trypanothione reductase by diaryl sulfide derivatives.,Saccoliti F, Angiulli G, Pupo G, Pescatori L, Madia VN, Messore A, Colotti G, Fiorillo A, Scipione L, Gramiccia M, Di Muccio T, Di Santo R, Costi R, Ilari A J Enzyme Inhib Med Chem. 2017 Dec;32(1):304-310. doi:, 10.1080/14756366.2016.1250755. PMID:28098499 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Trypanothione reductase

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