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Abstract: Understanding the differences between murine (m) and human (h) proteinase 3 (PR3) and neutrophil elastase (NE) is crucial for the interpretation of in vivo studies of inflammatory processes. We built structural models of mPR3 and mNE and analyzed their surface properties. We performed molecular dynamics (MD) simulations on several enzyme–peptide complexes to investigate their interaction patterns. The analysis of trajectories confirms that murine and human complexes have different interaction patterns with peptidic substrates. We provide a map of the binding sites of the murine proteases and suggest sequence motifs that we predict to be specific for mPR3 or mNE. [Copyright &y& Elsevier]

Cathepsin C (CatC, syn. Dipeptidyl peptidase I) is a lysosomal cysteine proteinase expressed in several tissues including inflammatory cells. This enzyme is important for maintaining multiple cellular functions and for processing immune cell-derived proteases. While mutations in the CatC gene were reported in Papillon-Lefèvre syndrome, a rare autosomal recessive disorder featuring hyperkeratosis and periodontitis, evidence from clinical and preclinical studies points toward pro-inflammatory effects of CatC in various disease processes that are mainly mediated by the activation of neutrophil serine proteinases. Moreover, tumor-promoting effects were ascribed to CatC. The aim of this review is to highlight current knowledge of the CatC as a potential therapeutic target in inflammatory disorders. [Display omitted] • Cathepsin C activates granule serine proteinases involved in inflammation. • Cathepsin C contributes to the pathogenesis of different acute and chronic diseases. • Potential of cathepsin C inhibition to ameliorate inflammation in preclinical models. • Need for studies evaluating CatC inhibitors repurposing in chronic inflammatory diseases. [ABSTRACT FROM AUTHOR]