Journal article

The Reaction Coordinate of a Bacterial GH47 alpha-Mannosidase: A Combined Quantum Mechanical and Structural Approach

Andrew J Thompson, Jerome Dabin, Javier Iglesias-Fernandez, Albert Ardevol, Zoran Dinev, Spencer J Williams, Omprakash Bande, Aloysius Siriwardena, Carl Moreland, Ting-Chou Hu, David K Smith, Harry J Gilbert, Carme Rovira, Gideon J Davies

Angewandte Chemie - International Edition | WILEY-V C H VERLAG GMBH | Published : 2012


Mannosides in the southern hemisphere: Conformational analysis of enzymatic mannoside hydrolysis informs strategies for enzyme inhibition and inspires solutions to mannoside synthesis. Atomic resolution structures along the reaction coordinate of an inverting α-mannosidase show how the enzyme distorts the substrate and transition state. QM/MM calculations reveal how the free energy landscape of isolated α-D-mannose is molded on enzyme to only allow one conformationally accessible reaction coordinate.

University of Melbourne Researchers


Awarded by Spanish Ministry of Economy and Competitiveness (MINECO)

Awarded by Generalitat de Catalunya

Awarded by Biotechnology and Biological Sciences Research Council

Funding Acknowledgements

We thank the UK Biotechnology and Biological Sciences Research Council (BBSRC), the Spanish Ministry of Economy and Competitiveness (MINECO, CTQ2011-25871), and the Generalitat de Catalunya (2009SGR-1309). A. S. thanks the Indo-French Centre for the Promotion of Advance Research (IFCPAR/CEFIPRA) for funding and for a postdoctoral fellowship (to O.B.). A. A. acknowledges a long-term fellowship from the European Molecular Biology Organization (EMBO). We acknowledge the computer support, technical expertise, and assistance provided by the Barcelona Supercomputing Center: Centro Nacional de Supercomputacion (BSC-CNS).