title: Quantum Mechanics/Molecular Mechanics Study of the Sialyltransferase Reaction Mechanism.
abstract: The sialyltransferase is an enzyme that transfers the sialic acid moiety from cytidine 5'-monophospho-N-acetyl-neuraminic acid (CMP-NeuAc) to the terminal position of glycans. To elucidate the catalytic mechanism of sialyltransferase, we explored the potential energy surface along the sialic acid transfer reaction coordinates by the hybrid quantum mechanics/molecular mechanics method on the basis of the crystal structure of sialyltransferase CstII. Our calculation demonstrated that CstII employed an SN1-like reaction mechanism via the formation of a short-lived oxocarbenium ion intermediate. The computational barrier height was 19.5 kcal/mol, which reasonably corresponded with the experimental reaction rate. We also found that two tyrosine residues (Tyr156 and Tyr162) played a vital role in stabilizing the intermediate and the transition states by quantum mechanical interaction with CMP.
authors.affiliation: Division of Materials Science, Graduate School of Nanobioscience, Yokohama City University , Seto 22-2, Kanazawa-ku, Yokohama 236-0027, Japan.
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Hamada
authors.affiliation: Division of Materials Science, Graduate School of Nanobioscience, Yokohama City University , Seto 22-2, Kanazawa-ku, Yokohama 236-0027, Japan.|Graduate School of Information Sciences, Hiroshima City University , Ozuka-Higashi 3-4-1, Asa-Minami-Ku, Hiroshima 731-3194, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kanematsu
authors.affiliation: Division of Materials Science, Graduate School of Nanobioscience, Yokohama City University , Seto 22-2, Kanazawa-ku, Yokohama 236-0027, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Tachikawa
mesh_terms: D011487:Protein Conformation; D011789:Quantum Theory; D012799:Sialyltransferases / Q000737:chemistry*
chemical_list: D012799:Sialyltransferases