Abstract
Lytic transglycosylases (LTs) catalyze the non-hydrolytic cleavage of the bacterial cell wall by an intramolecular transacetalization reaction. This reaction is critically and broadly important in modifications of the bacterial cell wall in the course of its biosynthesis, recycling, manifestation of virulence, insertion of structural entities such as the flagellum and the pili, among others. The first QM/MM analysis of the mechanism of reaction of an LT, that for the Escherichia coli MltE, is undertaken. The study reveals a conformational itinerary consistent with an oxocarbenium-like transition state, characterized by a pivotal role for the active-site glutamic acid in proton transfer. Notably, an oxazolinium intermediate, as a potential intermediate, is absent. Rather, substrate-assisted catalysis is observed through a favorable dipole provided by the N-acetyl carbonyl group of MurNAc saccharide. This interaction stabilizes the incipient positive charge development in the transition state. This mechanism coincides with near-synchronous acetal cleavage and acetal formation.
Highlights
The stereochemistry of Lytic transglycosylases (LTs) catalysis is overall retention with respect to the anomeric carbon of the MurNAc saccharide
membrane-bound lytic transglycosylase E (MltE) is a lipoprotein catalyst involved in the late stages of type VI secretion system assembly[11]
The dominant features of the Michaelis complex are the hydrogen-bonding pattern of E64 and the E1 conformation of the −1 MurNAc saccharide (see Supplementary Information for details: the hexose conformers are described as boat (B), chair (C), envelope (E, previously “sofa”), half-chair (H, sometimes called half-boat or twist), and skew (S, sometimes called twist-boat) conformations (Fig. 4), according to the Cremer and Pople nomenclature)[15,16,17]
Summary
Byungjin Byun[1], Kiran V. The dominant features of the Michaelis complex are the hydrogen-bonding pattern of E64 and the E1 conformation of the −1 MurNAc saccharide (see Supplementary Information for details: the hexose conformers are described as boat (B), chair (C), envelope (E, previously “sofa”), half-chair (H, sometimes called half-boat or twist), and skew (S, sometimes called twist-boat) conformations (Fig. 4), according to the Cremer and Pople nomenclature)[15,16,17]. The competence of this Michaelis complex was tested for its ability to traverse the full reaction coordinate across a 1D potential-energy surface (PES) scan (see Supplementary Information for details).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
