title: Mechanism of the glycosylation step catalyzed by human α-galactosidase: a QM/MM metadynamics study.
abstract: 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 D(N)*A(N)-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 (4)C(1) → [E(3)/(4)H(3)](++) → (1)S(3) along the reaction coordinate.
authors.affiliation: State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023, China.
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Pan
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Jing-Yao
authors.initials: JY
authors.lastname: Liu
mesh_terms: D055162:Biocatalysis; D006031:Glycosylation; D006801:Humans; D056004:Molecular Dynamics Simulation; D017434:Protein Structure, Tertiary; D011789:Quantum Theory; D013816:Thermodynamics; D000519:alpha-Galactosidase / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000519:alpha-Galactosidase