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Pseudomonas aeruginosa inhibitor of cysteine peptidases (PA-ICP) is a potent protein inhibitor of papain-like cysteine peptidases (CPs) identified in Pseudomonas aeruginosa, an opportunistic pathogenic bacteria that can cause severe infections in human. It belongs to the newly characterized natural CP inhibitors of the I42 family, designated the ICP family. The members of this family are present in some protozoa and bacterial pathogens. They can inhibit both parasite and mammalian CPs with high affinity and specificity. Whether the main biological function of the proteins in the pathogens is to regulate the hydrolytic activity of the organisms’ endogenous CPs or exogenous CPs so as to facilitate the pathogens’ invasion or survival is still under investigation. Although Pseudomonas aeruginosa contains a CP inhibitor, no CP genes are found in its genome, suggesting that the targets of PA-ICP may be exogenous. This hypothesis is supported by the presence of a putative secretion signal peptide at the N-terminus of PA-ICP which may be involved in exporting the protein to target exogenous CPs. In order to shed light on the biological function and inhibitory specificity of PA-ICP, the structure and backbone dynamics of this protein were characterised using NMR spectroscopy. In this project, the inhibitory activity of PA-ICP to a range of mammalian model CPs was also studied. Like its previously studied homologs, PA-ICP adopts an immunoglobulin fold comprised of seven β-strands. Three highly conserved sequence motifs located in mobile loop regions form the CP binding site. The inhibitor exhibits higher affinity toward the mammalian CP cathepsin L than cathepsins H and B. Homology modelling of the PA-ICP-cathspin L interaction based on the crystal structure of the chgasin-cathpsin L complex shows that PA-ICP may inhibit the peptidases by blocking the enzyme’s active site and that the interactions between chagasin and CPs may be conserved in PA-ICP-peptidase complexes. The specificity of the inhibitors may be determined by the relative flexibility of the loops bearing the binding site motifs and the electrostatic properties of certain residues near the binding sites.