Structural analysis of the catalytic site of AcCP-1, a cysteine proteinase secreted by the hookworm Ancylostoma caninum

Previously, we have reported that hookworms secrete cysteine proteinase activity that is capable of cleaving the cathepsin L-specific substrate Z-Phe-Arg-AMC. We have also reported the gene sequences of novel cathepsin B-like proteinases from hookworms, but have been unable to locate cathepsin L-like genes that could account for the presence of the cathepsin L activity in these parasites, Here we present an homology model for the secreted hookworm cysteine proteinase AcCP-1 based upon the crystal structure co-ordinates of human cathepsin B, The model predicts that substrate binding and specificity differs between AcCP-1 and cathepsin B, and demonstrates that AcCP-1 would preferentially cleave Phe-Arg over Arg-Arg. This thereby provides an explanation for our previous observations that the hookworm proteinase, while structurally cathepsin B-like, displays a cathepsin L-like substrate specificity.