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 proteinas e activity that is capable of cleaving the cathepsin L-specific substr ate Z-Phe-Arg-AMC. We have also reported the gene sequences of novel c athepsin B-like proteinases from hookworms, but have been unable to lo cate 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 pre dicts that substrate binding and specificity differs between AcCP-1 an d cathepsin B, and demonstrates that AcCP-1 would preferentially cleav e Phe-Arg over Arg-Arg. This thereby provides an explanation for our p revious observations that the hookworm proteinase, while structurally cathepsin B-like, displays a cathepsin L-like substrate specificity.