DFT studies on the β-glycosidase catalytic mechanism: The deglycosylation step

• Type: Article in International Scientific Journal
• Date: 2010

Authors

Natércia F. Braz (Author) FCUP; Maria J. Ramos (Author) FCUP; Pedro A. Fernandes (Author) FCUP

Journal

Title: Journal of Molecular Structure: THEOCHEM

Vol. 946 No. 1-3

Pages: 125-133

ISSN: 0166-1280

Publisher: Elsevier B.V.

Indexing

Scopus

Scientific classification

FOS: Engineering and technology > Chemical engineering

Other information

Abstract (EN): We have used computational methods to study the second step of the mechanism of reaction of retaining glycosidases in atomic detail. The model system included a simplified reaction center and a small substrate molecule to capture the intrinsic reactivity of the active-site motif. Using DFT calculations we were able to confirm and provide molecular-level detail to the general mechanism proposed in the literature for this family of enzymes. Of particular interest are the substrate distortion observed at the transition state and the dissociative character of the reaction mechanism. Different electrostatic environments were mimicked using a solvent continuum model and it was verified that a less specific surrounding gives a small, but measurable contribution for the reaction pathway. The performance of a wide variety of DFT functionals was also investigated. Density functionals of the different classes, namely, meta-generalized gradient approximation (meta-GGA), hybrid-GGA and hybrid-meta-GGA density functionals were tested. The DFT results were compared with high-level ab initio calculations carried out at the MP2, MP3, MP4 and QCISD(T) levels of theory.

Language: English

Type (Professor's evaluation): Scientific