4by0

Crystal structure of Trypanosoma cruzi CYP51 bound to the inhibitor (R)-N-(3-(1H-indol-3-yl)-1-oxo-1-(pyridin-4-ylamino)propan-2-yl)-3,3'- difluoro-(1,1'-biphenyl)-4-carboxamideCrystal structure of Trypanosoma cruzi CYP51 bound to the inhibitor (R)-N-(3-(1H-indol-3-yl)-1-oxo-1-(pyridin-4-ylamino)propan-2-yl)-3,3'- difluoro-(1,1'-biphenyl)-4-carboxamide

Structural highlights 4by0 is a 2 chain structure with sequence from Trycr. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: , Activity: Sterol 14-demethylase, with EC number 1.14.13.70 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Sterol 14alpha-demethylase (CYP51) is an important therapeutic target for fungal and parasitic infections due to its key role in the biosynthesis of ergosterol, an essential component of the cell membranes of these pathogenic organisms. We report the development of potent and selective d-tryptophan-derived inhibitors of T. cruzi CYP51. Structural information obtained from the cocrystal structure of CYP51 and (R)-2, which is >1000-fold more potent than its enantiomer (S)-1, was used to guide design of additional analogues. The in vitro efficacy data presented here for (R)-2-(R)-8, together with preliminary in vitro pharmacokinetic data suggest that this new CYP51 inhibitor scaffold series has potential to deliver drug candidates for treatment of T. cruzi infections. R-Configuration of 4-Aminopyridyl-Based Inhibitors of CYP51 Confers Superior Efficacy Against Trypanosoma cruzi.,Choi JY, Calvet CM, Vieira DF, Gunatilleke SS, Cameron MD, McKerrow JH, Podust LM, Roush WR ACS Med Chem Lett. 2014 Jan 22;5(4):434-9. doi: 10.1021/ml500010m. eCollection, 2014 Apr 10. PMID:24900854 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

spinqualitylabelsall models 4by0, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image