Sokoine University of Agriculture

Propeptide-like cysteine protease inhibitors: Structural properties, Mechanisms of inhibition and emerging roles in biological tissues

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dc.contributor.author Luziga, C.
dc.contributor.author Nga, B.
dc.contributor.author Yamamoto, Y.
dc.date.accessioned 2020-09-29T06:26:34Z
dc.date.available 2020-09-29T06:26:34Z
dc.date.issued 2016-05-01
dc.identifier.citation Luziga C, Nga BT, Yoshimi Y. (2016). Propeptide-like cysteine protease inhibitors: Structural properties, Mechanisms of inhibition and emerging roles in biological tissues. Current Topics in Peptide & Protein Research. 17:71-82. en_US
dc.identifier.uri http://www.suaire.sua.ac.tz/handle/123456789/3195
dc.description Current topics in Peptide & Protein research, 2016; 17 (2016): 71-82 en_US
dc.description.abstract Propeptides of cysteine proteases including papain and cathepsins B, K, L, and S are selective inhibitors of their cognate cysteine proteases. A new class of endogenous inhibitors homologous to the propeptide regions of cysteine proteases has been identified and characterized in the past few decades. These include the mouse cytotoxic T-lymphocyte antigen-2 (CTLA-2), Bombyx cysteine proteinase inhibitor (BCPI), Drosophila crammer, and salmon salarin. They have been categorized as I29 (CTLA family) in the MEROPS peptidase database. In this review, we summarized experimental findings on their molecular forms, inhibition mechanisms, and biological functions. The overall properties of these inhibitors, molecular structures and inhibition mechanisms were found to be similar to those of propeptides of cysteine proteases. CTLA-2 has been shown to possess a unique inhibition mechanism by blocking its cognate enzyme, cathepsin L, through oxidizing the active thiol residue of the enzyme with its own thiol residue. The divergent biological functions of these inhibitors have been determined based on their inhibitory activities towards cathepsin L-like cysteine proteases. CTLA-2 is strongly expressed in the placenta, and may play roles in implantation and decidualization. It is also an inducer of Treg cells in the eyes, and has been shown to induce apoptosis in murine T-lymphoma cells and cardiac fibroblasts. In the brain, CTLA-2 transcript is strongly expressed in neuronal cell bodies while the protein is localized in dendrites and fibre bundles. BCPI has been demonstrated to exhibit anti-parasitic activity and thus thought to act as a negative regulator of silk gland histolysis. Crammer has been identified in mushroom bodies (brain) of Drosophila melanogaster as one of the proteins essential for long-term memory formation through regulation of cathepsin activity in the insect. These findings suggest that the inhibitors are novel proteins that participate in various physiological actions in different organisms. Their emerging roles in normal biological tissues, diseases and as potential targets for drug development are discussed in detail. en_US
dc.publisher Current Topics in Peptide & Protein Research. en_US
dc.subject Inhibitor en_US
dc.subject Cysteine protease en_US
dc.subject PropeCTLA-2 en_US
dc.subject BCPI en_US
dc.subject Crammer en_US
dc.title Propeptide-like cysteine protease inhibitors: Structural properties, Mechanisms of inhibition and emerging roles in biological tissues en_US
dc.type Article en_US
dc.url http://researchtrends.net/tia/abstract.asp?in=0&vn=17&tid=26&aid=5919&pub=2016&type=3 en_US


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