O-/N-/S-specificity in glycosyltransferase catalysis: From mechanistic understanding to engineering
| Autor: | Gonzalo N. Bidart, Joan Coines, Ditte Hededam Welner, Kshatresh Dutta Dubey, Birte Svensson, John E. Dueber, David Teze, Carme Rovira, Paul D. Adams, Folmer Fredslund |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Stereochemistry
Glycoconjugate Carbohydrates 010402 general chemistry 01 natural sciences Catalysis N-gycosylation N-linked glycosylation Glycosyltransferase Molecule S-glycosylation chemistry.chemical_classification O-glycosylation biology 010405 organic chemistry Glycosyltransferases Glycosidic bond General Chemistry Acceptor 0104 chemical sciences Enzymes Enzyme chemistry biology.protein Quantum mechanics/molecular mechanics |
| Zdroj: | Tezé, D, Coines, J, Fredslund, F, Dubey, K D, Bidart, G N, Adams, P D, Dueber, J E, Svensson, B, Rovira, C & Welner, D H 2021, ' O-/N-/S-specificity in glycosyltransferase catalysis: From mechanistic understanding to engineering ', ACS Catalysis, vol. 11, no. 3, pp. 1810-1815 . https://doi.org/10.1021/acscatal.0c04171 |
| DOI: | 10.1021/acscatal.0c04171 |
| Popis: | Glycosyltransferases (GTs) catalyze the formation of glycosidic bonds in carbohydrates and glycoconjugates, with various outcomes depending not only on the acceptor molecules they bind but also on the type of glycosidic bond they form (C−O, C−N, C−S, or C−C). Here we show that the glucosyltransferase UGT1 from the indigo plant Polygonum tinctorium catalyzes either N-, O-, or S-glycosylation with similar rates. We solve the structure of the enzyme in complex with its donor and acceptor substrates and elucidate the molecular basis of N-, O-, and S-specificities using experimental mutagenesis and QM/MM simulations, revealing distinct mechanisms for N-, O-, and S-glycosylation. We also show that the active site can be engineered to increase or favor one of the three glycosylation activities over another. These results will foster the design of more active and specific enzyme variants for production of glycosides. |
| Databáze: | OpenAIRE |
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