title: Reaction Mechanisms in Carbohydrate-Active Enzymes: Glycoside Hydrolases and Glycosyltransferases. Insights from ab Initio Quantum Mechanics/Molecular Mechanics Dynamic Simulations.
abstract: Carbohydrate-active enzymes such as glycoside hydrolases (GHs) and glycosyltransferases (GTs) are of growing importance as drug targets. The development of efficient competitive inhibitors and chaperones to treat diseases related to these enzymes requires a detailed knowledge of their mechanisms of action. In recent years, sophisticated first-principles modeling approaches have significantly advanced in our understanding of the catalytic mechanisms of GHs and GTs, not only the molecular details of chemical reactions but also the significant implications that just the conformational dynamics of a sugar ring can have on these mechanisms. Here we provide an overview of the progress that has been made in the past decade, combining molecular dynamics simulations with density functional theory to solve these sweet mysteries of nature.
authors.affiliation: †Departament de Química Orgànica and Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Ardèvol
authors.affiliation: †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.
authors.forename: Carme
authors.initials: C
authors.lastname: Rovira
mesh_terms: D000818:Animals; D002236:Carbohydrate Conformation; D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000737:chemistry; D006026:Glycoside Hydrolases / Q000737:chemistry / Q000378:metabolism*; D016695:Glycosyltransferases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D011789:Quantum Theory; D013816:Thermodynamics
chemical_list: D002241:Carbohydrates; D016695:Glycosyltransferases; D006026:Glycoside Hydrolases