The reaction mechanism of retaining glycosyltransferases. (9th February 2016)

• Record Type: Journal Article
• Authors: Ardèvol, Albert; Iglesias-Fernández, Javier; Rojas-Cervellera, Víctor; Rovira, Carme
• Is Part Of: Biochemical Society transactions. Volume 44:Number 1(2016)
• Page Start: 51
• Page End: 60
• Publication Date: 2016-02-09
• Subjects: ab initio molecular dynamics -- enzyme catalysis -- glycosyltransferases -- metadynamics -- quantum mechanics/molecular mechanics -- retention of configuration; Biochemistry -- Congresses; 572
• DOI: 10.1042/BST20150177
• Languages: English
• ISSNs: 0300-5127

Abstract

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 SN i (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.