Molecular characterization of a family 5 glycoside hydrolase suggests an induced-fit enzymatic mechanism

• Autor(a) principal: Liberato, Marcelo V.
• Data de Publicação: 2016
• Outros Autores: Silveira, Rodrigo L., Prates, Erica T., Araujo, Evandro A. de, Pellegrini, Vanessa O. A., Camilo, Cesar M., Kadowaki, Marco A., Neto, Mario de O. [UNESP], Popov, Alexander, Skaf, Munir S., Polikarpov, Igor
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1038/srep23473; http://hdl.handle.net/11449/158786

Glycoside hydrolases (GHs) play fundamental roles in the decomposition of lignocellulosic biomaterials. Here, we report the full-length structure of a cellulase from Bacillus licheniformis (BlCel5B), a member of the GH5 subfamily 4 that is entirely dependent on its two ancillary modules (Ig-like module and CBM46) for catalytic activity. Using X-ray crystallography, small-angle X-ray scattering and molecular dynamics simulations, we propose that the C-terminal CBM46 caps the distal N-terminal catalytic domain (CD) to establish a fully functional active site via a combination of large-scale multidomain conformational selection and induced-fit mechanisms. The Ig-like module is pivoting the packing and unpacking motions of CBM46 relative to CD in the assembly of the binding subsite. This is the first example of a multidomain GH relying on large amplitude motions of the CBM46 for assembly of the catalytically competent form of the enzyme.