The catalytic mechanism of retaining glycosyltransferases (ret-GTs) remains a controversial issue in glycobiology. By analogy to the well-established mechanism of retaining glycosidases, it was first suggested that ret-GTs follow a double-displacement mechanism. However, only family 6 GTs exhibit a putative nucleophile protein residue properly located in the active site to participate in catalysis, prompting some authors to suggest an unusual single-displacement mechanism [named as front-face or SNi (substitution nucleophilic internal)-like]. This mechanism has now received strong support, from both experiment and theory, for several GT families except family 6, for which a double-displacement reaction is predicted. In the last few years, we have uncovered the molecular mechanisms of several retaining GTs by means of quantum mechanics/molecular mechanics (QM/MM) metadynamics simulations, which we overview in the present work.
- ab initio molecular dynamics
- enzyme catalysis
- quantum mechanics/molecular mechanics
- retention of configuration
Carbohydrate Active Enzymes in Medicine and Biotechnology: Held at University of St Andrews, Fife, Scotland, U.K., 19–21 August 2015.
- collective variable;
- density functional theory;
- free-energy landscape;
- GalNAc-transferase 2;
- glycoside hydrolase;
- lipopolysaccharyl α-galactosyltransferase;
- trehalose-6-phosphate synthase;
- substitution nucleophilic internal;
- transition state
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