Catalytides derived from the Box A region in the ANA/BTG3 protein cleave amyloid-β fragment peptide

Yusuke Hatakawa; Rina Nakamura; Motomi Konishi; Toshiyasu Sakane; Motoaki Saito; Toshifumi Akizawa

doi:10.1016/j.heliyon.2019.e02454

Catalytides derived from the Box A region in the ANA/BTG3 protein cleave amyloid-β fragment peptide

Heliyon. 2019 Sep 24;5(9):e02454. doi: 10.1016/j.heliyon.2019.e02454. eCollection 2019 Sep.

Authors

Yusuke Hatakawa¹, Rina Nakamura^{2

3}, Motomi Konishi⁴, Toshiyasu Sakane¹, Motoaki Saito³, Toshifumi Akizawa^{2

3}

Affiliations

¹ Pharmaceutical Technology, Kobe Pharmaceutical University, 4-19-1, Motoyamakita, Higashinada, Kobe, 658-8558, Japan.
² O-Force Co., Ltd, 3454 Irino Kuroshio-cho, Hata-gun, Kochi 789-1931, Japan.
³ Laboratory of Pharmacology, School of Medicine, Kochi University, Kohasu, Oko-cho, Nankoku, Kochi, 783-0047, Japan.
⁴ Laboratory of Clinical Analytical Chemistry, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.

Abstract

We have recently reported about shorter proteolytic peptides termed Catalytide as general name. JAL-TA9 (YKGSGFRMI), a fragment peptide derived from Box A region of Tob1 protein, is the first Catalytide and cleaves Aβ42 and its fragment peptides. Herein, we demonstrate the enzymatic properties of ANA-TA9 corresponding region to JAL-TA9 in ANA/BTG3 protein. ANA-TA9 showed the auto-proteolytic activity and cleaved 3 kinds of synthetic fragment peptides derived from Aβ42, especially on the central region of Aβ42 with a serine protease like activity. Interestingly, 2 kinds of components, ANA-SA5 (SKGQA) and ANA-YA4 (YRMI), also showed similar proteolytic activity. These results indicate that ANA-TA9 is composed of two different Catalytides.

Keywords: ANA/BTG3; Alzheimer's disease; Amyloid-β peptide; Analytical chemistry; Biochemistry; Biophysical chemistry; Biotechnology; Box A region; Catalytide; Chromatography; Developmental biology; Hydrolase activity; Molecular biology; Molecular modeling; Peptides; Structural biology; Tob/BTG.