Fig. 3

Assessment of structural conservation in Clonorchis sinensis NPC2 and NPC2-like proteins. Predicted structures of 21 C. sinensis NPC2 and NPC2-like proteins were aligned to assess conservation relative to two reference NPC2 protein structures (2HKA and 3WEA). a Alignment of NPC2 and NPC2-like sequences and conserved barrel with seven-stranded β-sandwich folds (shown in green) fixed by three disulfide bonds (Cys-8-Cys-121, Cys-23-Cys-28, and Cys-74-Cys-80; indicated by black lines below the alignment). b Positioning of loops in C. sinensis NPC2 models was modelled on a closed sterol binding pocket. Conserved residues are shown in red, variable residues are shown in blue and fewer variable residues are shown in white. c Hydrophobic tunnel from an opening created by three β-sandwich loops and highlighting three amino acid residues important for binding cholesterol (Val-105, i; Tyr-109, ii; and Phe-73, iii). d A fully open pocket in the presence of bound cholesterol sulphate (orange)