Mechanism of the Glycosylation Step Catalyzed by Human α-Galactosidase: A QM/MM Metadynamics Study
2013
Pan, Xiao-Liang | Liu, Wei | Liu, Jing-Yao
The enzyme α-galactosidase (α-GAL), a member of glycoside hydrolase family 27, catalyzes the removal of a nonreducing terminal α-galactose residue from polysaccharides, glycolipids, and glycopeptides. α-GAL is believed to have the double displacement retaining reaction mechanism. In this work, the glycosylation step catalyzed by human α-GAL was computationally simulated with quantum mechanics/molecular mechanics metadynamics. Our simulations show that the overall catalytic mechanism follows a DN*AN-like mechanism, and the transition state has a oxocarbenium ion like character with a partially formed double bond between the ring oxygen and C5′ carbon atoms. In addition, the galactosyl ring of the substrate follows a conformational itinerary of ⁴C₁ → [E₃/⁴H₃]⧧ → ¹S₃ along the reaction coordinate.
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