Ardèvol Albert, Iglesias-Fernández Javier, Rojas-Cervellera Víctor, Rovira Carme
Departament de Química Orgànica and Institut de Química Teòrica i Computacional (IQTCUB), Universitat de Barcelona, Martí i Franquès 1, 08028 Barcelona, Spain.
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
Biochem Soc Trans. 2016 Feb;44(1):51-60. doi: 10.1042/BST20150177.
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.
保留型糖基转移酶（ret-GTs）的催化机制在糖生物学中仍然是一个有争议的问题。类比于已确立的保留型糖苷酶机制，最初有人提出ret-GTs遵循双取代机制。然而，只有6家族GTs在活性位点有一个合适定位的推定亲核蛋白残基参与催化，这促使一些作者提出一种不同寻常的单取代机制[称为正面或类SNi（亲核取代内型）机制]。除了预测为双取代反应的6家族外，这种机制现在已得到来自实验和理论的有力支持，适用于几个GT家族。在过去几年中，我们通过量子力学/分子力学（QM/MM）元动力学模拟揭示了几种保留型GTs的分子机制，我们将在本工作中对此进行概述。
