2015 journal article

How Cellulose Elongates-A QM/MM Study of the Molecular Mechanism of Cellulose Polymerization in Bacterial CESA

JOURNAL OF PHYSICAL CHEMISTRY B, 119(22), 6525–6535.

co-author countries: United States of America 🇺🇸
MeSH headings : Biocatalysis; Carbohydrate Conformation; Cellulose / chemistry; Cellulose / metabolism; Enzyme Activation; Glucose / chemistry; Glucose / metabolism; Glucosyltransferases / chemistry; Glucosyltransferases / metabolism; Glycosylation; Molecular Dynamics Simulation; Polymerization; Protein Conformation; Protons; Quantum Theory; Rhodobacter / enzymology; Uridine Diphosphate / chemistry; Uridine Diphosphate / metabolism; Water / chemistry
Source: Web Of Science
Added: August 6, 2018

The catalytic mechanism of bacterial cellulose synthase was investigated by using a hybrid quantum mechanics and molecular mechanics (QM/MM) approach. The Michaelis complex model was built based on the X-ray crystal structure of the cellulose synthase subunits BcsA and BcsB containing a uridine diphosphate molecule and a translocating glucan. Our study identified an SN2-type transition structure corresponding to the nucleophilic attack of the nonreducing end O4 on the anomeric carbon C1, the breaking of the glycosidic bond C1-O1, and the transfer of proton from the nonreducing end O4 to the general base D343. The activation barrier found for this SN2-type transition state is 68 kJ/mol. The rate constant of polymerization is estimated to be ∼8.0 s(-1) via transition state theory. A similar SN2-type transition structure was also identified for a second glucose molecule added to the growing polysaccharide chain, which aligned with the polymer 180° rotated compared to the initially added unit. This study provides detailed insights into how cellulose is extended by one glucose molecule at a time and how the individual glucose units align into cellobiose repeating units.