Aromatic residues in N-terminal domain of archaeal trehalase affect the folding and activity of catalytic domain
Year: 2024
Type: article
Abstract: Trehalase (trehalose-glucohydrolase, EC 3.2.1.28) hydrolyzes trehalose to yield two glucose molecules, and plays important roles in modulating the concentration of trehalose in living cells. Trehalose functions as a source of carbon energy and as a protector against various stress conditions, such as desiccation, osmotic stress, and oxidation (Elbein et al. 2003 ). In addition, this disaccharide is widely applied in the field of pharmaceuticals and the food and cosmetic industries (Argüelles 2000 ; Higashiyama 2002 ; Ohtake and Wang 2011 ), because trehalose induces mTOR-independent autophagy (Sarkar et al. 2007 ), inhibits the aggregation of pathogenetic factors of Alzheimer’s disease (AD), such as β-amyloid 40 and tau protein, and reduces their cytotoxicity in vitro (Liu et al. 2005 ; Kruger et al. 2012 ). Trehalases belonging to the glycoside hydrolase 37 (GH37), GH65, and GH15 families (Carbohydrate-Active enZyme database, CAZy, http://www.cazy.org/ ) have been noted. Recently, we found two archaeal trehalose-hydrolyzing enzymes that belong to the GH15 family, i.e., Tvn1315 and Ta0286, which originate from the thermoacidophilic archaea Thermoplasma volcanium and Thermoplasma acidophilum , respectively (Sakaguchi et al. 2015 ). The archaeal trehalases show higher similarity to GH15 family bacterial glucoamylase (GA) than GH37 and GH65 enzymes. Most GH15 family enzymes has additional domain(s) at the N-terminal and/or C-terminal sides of their own catalytic domains (CDs). The GH15 family bacterial GA [α-(1 → 4)-D-glucan glucohydrolase, EC 3.2.1.3] which acts on α-(1 → 4) glucosidic linkages to release β-D-glucose from the nonreducing end of substrates possesses an N-terminal domain with a β-sandwich structure (BD) and a C-terminal catalytic domain (CD) with an (α/α) 6 -barreled structure (Aleshin et al. 2003 ). Based on the sequence similarities to bacterial GA and models built using an Alphafold2 protein structure prediction method (Jumper et al. 2021 , Fig. S1 ), archaeal GH15 trehalases may have an N-terminal BD and a C-terminal CD. A CD with an (α/α) 6 -barreled structure is a common feature of GH15, GH37 and GH65 trehalases.
Authors: Takumi Sakoh, Nagisa Satoh, Yumeka Domon, Maho Nakamura, Masao Kawakita, Masayoshi Sakaguchi
Institutions: Kogakuin University, Kokugakuin University
Language: English
Subfield: Biotechnology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,390
OpenAlex ID: W4401595538