The catalytic kinetics of chicken transthyretin towards human Aβ1-42

Abstract

The novel property of transthyretin (TTR) as a protease has been proposed to be significant. However, the study of TTR proteolysis properties has not been completely elucidated. Herein, we first report the catalytic activity of chicken TTR from plasma determined by using fluorescently labeled amyloid beta 1-42 peptide (Aβ_1-42), and compared it with human TTR (human TTR) from plasma and recombinant Crocodylus porosus TTR. The enzyme kinetic study revealed that the affinity for Aβ_1-42 of chicken TTR and C. porosus TTR (K_M values were 12.72 ± 0.27 μM and 16.21 ± 0.02 μM, respectively) were significantly lower than human TTR (K_M was 43.05 ± 0.39 μM). In addition, the catalytic efficiency of chicken TTR (K_cat/K_M was 310,386.87 ± 13,627.12 M^-1 s^-1) was 4.3 and 5.5 folds higher than those of C. porosus TTR and human TTR (K_cat/K_M were 72,893.80 ± 355.74 M^-1 s^-1 and 56,519.12 ± 5009.50 M^-1 s^-1, respectively), respectively. These results does not only indicated the relationship between structure and the proteolytic activity of TTR, but also suggested a potential development of TTR as a therapeutic anti-Aβ agent.

Keywords: Amyloid beta; Catalytic kinetics; Proteolytic activity; Transthyretin.