Novel Cysteine Proteinase Inhibitors Homologous to the Proregions of Cysteine Proteinases
Y. Yamamoto, M. Kurata, S. Watabe, R. Murakami and S. Y. Takahashi
Affiliation: Laboratory ofBiochemistry and Radiation Biology, Department of Veterinary Sciences, Faculty of Agriculture, Yamaguchi University, Yamaguchi 753-8515, Japan
Keywords: cysteine proteinase inhibitors homologous, cysteine proteinases, propeptide inhibitors, propeptide-like inhibitors, pleurotus ostreatus
Propeptides of papain-like cysteine proteinases such as papain, cathepsins B, L and S are potent inhibitors of their cognate cysteine proteinases with Ki values in the nanomolar range, and they exhibit highest inhibition selectivity for enzymes from which they originate. Recent studies have identified novel inhibitor proteins that are homologous to the proregions of papain-like cysteine proteinases. Mouse activated T-lymphocytes express cytotoxic T-lymphocyte antigen (CTLA-2), which is homologous to the proregion of mouse cathepsin L. CTLA-2 exhibits inhibitory activities to several cysteine proteinases. We have also identified a similar propeptide-like cysteine proteinase inhibitor, Bombyx cysteine proteinase inhibitor (BCPI), in the silkmoth Bombyx mori. BCPI is a slow and tight binding inhibitor of cathepsin L-like cysteine proteinases with Ki values in picomolar range, and the inhibition is highly selective towards these proteinases just like the propeptides. Recent genome analyses have shown the expression of similar propeptide-like proteins in Drosophila and rat, suggesting the presence of a novel class of cysteine proteinase inhibitors in a variety of organisms. Studies of the gene structures and phylogenetic analysis have shown that genes of the propeptide-like cysteine proteinase inhibitors have emerged from ancestor genes of their parental enzymes.
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