Engineering and Structural Insights of a Novel BBI-like Protease Inhibitor Livisin from the Frog Skin Secretion |
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| Authors: | Jie Yang Chengliang Tong Junmei Qi Xiaoying Liao Xiaokun Li Xu Zhang Mei Zhou Lei Wang Chengbang Ma Xinping Xi Tianbao Chen Yitian Gao Di Wu |
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| Institution: | 1.Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325015, China; (J.Y.); (C.T.); (X.L.);2.College of Life and Environmental Science, Wenzhou University, Wenzhou 325035, China; (J.Q.); (X.L.); (X.Z.);3.Natural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT7 1NN, UK; (M.Z.); (L.W.); (C.M.); (X.X.); (T.C.) |
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| Abstract: | The Bowman–Birk protease inhibitor (BBI) family is a prototype group found mainly in plants, particularly grasses and legumes, which have been subjected to decades of study. Recently, the discovery of attenuated peptides containing the canonical Bowman–Birk protease inhibitory motif has been detected in the skin secretions of amphibians, mainly from Ranidae family members. The roles of these peptides in amphibian defense have been proposed to work cooperatively with antimicrobial peptides and reduce peptide degradation. A novel trypsin inhibitory peptide, named livisin, was found in the skin secretion of the green cascade frog, Odorrana livida. The cDNA encoding the precursor of livisin was cloned, and the predicted mature peptide was characterized. The mature peptide was found to act as a potent inhibitor against several serine proteases. A comparative activity study among the native peptide and its engineered analogs was performed, and the influence of the P1 and P2′ positions, as well as the C-terminal amidation on the structure–activity relationship for livisin, was illustrated. The findings demonstrated that livisin might serve as a potential drug discovery/development tool. |
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| Keywords: | protease inhibitor antimicrobial peptide natural product skin secretions animal venoms |
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