title: The reaction mechanism of retaining glycosyltransferases.
abstract: 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.
authors: Departament de Química Orgànica and Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain.
authors: Albert
authors: A
authors: Ardèvol
authors: Departament de Química Orgànica and Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain.
authors: Javier
authors: J
authors: Iglesias-Fernández
authors: Departament de Química Orgànica and Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain.
authors: Víctor
authors: V
authors: Rojas-Cervellera
authors: Departament de Química Orgànica and Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys, 23, 08018 Barcelona, Spain c.rovira@ub.edu.
authors: Carme
authors: C
authors: Rovira
mesh_terms: D000818:Animals; D006027:Glycosides / Q000737:chemistry / Q000378:metabolism; D006031:Glycosylation; D016695:Glycosyltransferases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D011789:Quantum Theory
chemical_list: D006027:Glycosides; D016695:Glycosyltransferases
keywords: ab initio molecular dynamics; enzyme catalysis; glycosyltransferases; metadynamics; quantum mechanics/molecular mechanics; retention of configuration