How Cellulose Elongates--A QM/MM Study of the Molecular Mechanism of Cellulose Polymerization in Bacterial CESA.
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.
†Department of Geosciences, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.
Hui
H
Yang
‡Center for Membrane Biology and Department of Molecular Physiology and Biological Physics, University of Virginia School of Medicine, Charlottesville, Virginia 22908, United States.
Jochen
J
Zimmer
§Department of Materials Science and Engineering, North Carolina State University, Raleigh, North Carolina 27695, United States.
Yaroslava G
YG
Yingling
†Department of Geosciences, The Pennsylvania State University, University Park, Pennsylvania 16802, United States.
James D
JD
Kubicki
D055162:Biocatalysis; D002236:Carbohydrate Conformation; D002482:Cellulose / Q000737:chemistry* / Q000378:metabolism; D004789:Enzyme Activation; D005947:Glucose / Q000737:chemistry / Q000378:metabolism; D005964:Glucosyltransferases / Q000737:chemistry / Q000378:metabolism*; D006031:Glycosylation; D056004:Molecular Dynamics Simulation; D058105:Polymerization; D011487:Protein Conformation; D011522:Protons; D011789:Quantum Theory; D016992:Rhodobacter / Q000201:enzymology; D014530:Uridine Diphosphate / Q000737:chemistry / Q000378:metabolism; D014867:Water / Q000737:chemistry
D011522:Protons; D014867:Water; D014530:Uridine Diphosphate; D002482:Cellulose; D005964:Glucosyltransferases; C478648:cellulose synthase; D005947:Glucose