Vibrio cholerae produces a large multifunctional protein that undergoes autoproteolytic processing catalyzed by its cysteine protease domain (CPD) to release the cytopathic domains within the eukaryotic host cell cytoplasm. The CPD is activated after translocation into the host cell by the binding of inositol hexaphosphate (InsP6, red in the picture). One of the sites of proteolysis is at the N-terminus of the CPD. X-Ray crystallographic structure determination of the pro-form of a catalytically inactive mutant (C3568S) CPD reveals the structural basis for the InsP6 activation and the mechanism of proteolytic processing. The 1.8Å crystal structure shows that the CPD is a caspase-like protein that has the leucine (purple) of its N-terminal cleavage site bound in a hydrophobic specificity pocket and the scissile peptide bond located between the serine that was substituted for the essential cysteine and the conserved histidine residue (both shown with magenta carbon atoms). The InsP6 activating ligand is bound by a number of positively charged lysine and arginine residues from the N-terminal region (blue), the main body of the CDP (yellow) and the C-terminal region (green). Related toxins with Cysteine Protease Domains, but other cytopathic domains, occur in a number of other gram-negative bacteria.