L-balenine inhibits the catalytic activity of Pin1, a peptidyl prolyl cis/trans-isomerase

• Published in: Personalized Medicine Universe Vol. 9; pp. 51 - 58
• Main Authors: Takahashi, Katsuhiko, Uchida, Takafumi, Higashi, Nobuaki, Kamei, Junzo
• Format: Journal Article
• Language: English
• Published: International Society of Personalized Medicne 31.10.2020
• Subjects: Balenine; Imidazole peptide; Peptidyl prolyl cis/trans-isomerase; Pin1
• ISSN: 2186-4969; 2186-4950
• DOI: 10.46459/pmu.2020003

Purpose: Pin1 is a peptidyl prolyl cis/trans-isomerase (PPIase) that regulates phosphorylated protein function by cis-trans-isomerization. Pin1 catalytic activity has been associated with the pathogenesis of cancer, asthma, neurodegenerative diseases, nonalcoholic steatohepatitis, and viral infections. Recently, imidazole dipeptide molecules from natural products have attracted interest as functional food components. Here, we evaluated the effects of natural imidazole dipeptides on the PPIase activity of Pin1 to identify novel Pin1 inhibitors.Methods: PPIase catalytic activity of Pin1 was measured using chymotrypsin-coupled isomer specific protein degradation. The test substance was preincubated with recombinant Pin1 to form their complex.Results: Our results showed that among the imidazole dipeptide molecules, L-balenine, and not L-anserine and L-carnosine, reduced the PPIase activity of Pin1. Both β-alanine and 1-methyl-L-histidine obtained by hydrolysis of L-balenine did not affect Pin1 PPIase activity. These results suggested that the structure of L-balenine allows it to occupy the active site of the Pin1 enzyme.Conclusion: Among imidazole dipeptides from natural products, L-balenine inhibited the PPIase catalytic activity of Pin1.