Combined Inhibitor Free-Energy Landscape and Structural Analysis Reports on the Mannosidase Conformational Coordinate (pages 1087–1091)
Dr. Rohan J. Williams, Javier Iglesias-Fernández, Dr. Judith Stepper, Adam Jackson, Dr. Andrew J. Thompson, Dr. Elisabeth C. Lowe, Prof. Jonathan M. White, Prof. Harry J. Gilbert, Prof. Carme Rovira, Prof. Gideon J. Davies and Prof. Spencer J. Williams
Article first published online: 11 DEC 2013 | DOI: 10.1002/anie.201308334
Shipshape inhibitors: Quantum mechanical calculations of the free-energy landscape (see figure) of the glycosidase transition-state mimics isofagomine and mannoimidazole reveals that only the latter is energetically poised to report upon the mannosidase transition-state conformation. X-ray structures of β-mannanases from different families reveal they both adopt a boat conformation, thus allowing unification of the enzymatic conformational itinerary of a range of diverse α- and β-mannosidases.