The first structure-function study of GH151 alpha-l-fucosidase uncovers new oligomerization pattern, active site complementation, and selective substrate specificity

0560263 - BTÚ 2023 RIV GB eng J - Článek v odborném periodiku
Koval'ová, Terezia - Koval, Tomáš - Stránský, Jan - Kolenko, Petr - Dušková, Jarmila - Švecová, Leona - Vodickova, P. - Spiwok, V. - Benešová, E. - Lipovová, P. - Dohnálek, Jan
The first structure-function study of GH151 alpha-l-fucosidase uncovers new oligomerization pattern, active site complementation, and selective substrate specificity.
FEBS Journal. Roč. 289, č. 16 (2022), č. článku 16387. ISSN 1742-464X. E-ISSN 1742-4658
Grant CEP: GA MŠMT(CZ) LM2015043; GA MŠMT EF15_003/0000447; GA MŠMT(CZ) EF16_013/0001776; GA MŠMT(CZ) ED1.1.00/02.0109; GA MŠMT(CZ) LM2018127
Institucionální podpora: RVO:86652036
Klíčová slova: active site complementation * crystal structure * gh151 * alpha-l-fucosidase
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 5.4, rok: 2022
Způsob publikování: Omezený přístup
https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.16387

Fucosylated compounds are abundantly present in nature and are associated with many biological processes, therefore carrying great potential for use in medicine and biotechnology. Efficient ways to modify fucosylated compounds are still being developed. Promising results are provided by glycosyl hydrolases with transglycosylating activities, such as alpha-l-fucosidase isoenzyme 2 from Paenibacillus thiaminolyticus (family GH151 of Carbohydrate-Active enZYmes). Currently, there is no 3D structure representing this glycoside hydrolase family and only a few members have been investigated. Here, we present the first structure-function study of a GH151 member, providing the key insights into its specific oligomerization and active site properties. According to the crystal structure, small-angle X-ray scattering data and catalytic investigation, this enzyme functions as a tetramer of a new type and represents the second known case of active site complementation among all alpha-l-fucosidases. Mutation of the active site-complementing residue histidine 503 to alanine confirmed its influence on alpha-l-fucosidase activity and, specifically, on substrate binding. Several unique features of GH151 family alpha-l-fucosidases were revealed, including the oligomerization pattern, active site accessibility and complementation, and substrate selectivity. Some common properties of GH151 glycosyl hydrolases then would be the overall three-domain structure and conservation of the central domain loop 2 function, including its complementation role and the formation of the carbohydrate-binding platform in the active site vicinity.
Trvalý link: https://hdl.handle.net/11104/0340729