Insights into Glucose-6-phosphate Allosteric Activation of β-Glucosidase A.

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TitleInsights into Glucose-6-phosphate Allosteric Activation of β-Glucosidase A.
Publication TypeJournal Article
Year of Publication2021
AuthorsGomes, AA, Da Silva, GF, Lakkaraju, SK, Guimarães, BGomes, Mackerell, AD, Magalhães, Mde Lourdes
JournalJ Chem Inf Model
Date Published2021 Apr 05
ISSN1549-960X
Abstract

Second-generation ethanol production involves the use of agricultural and forestry waste as feedstock, being an alternative to the first-generation technology as it relies on low-cost abundant residues and does not affect food agriculture. However, the success of second-generation biorefineries relies on energetically efficient processes and effective enzyme cocktails to convert cellulose into fermentable sugars. β-glucosidases catalyze the last step on the enzymatic hydrolysis of cellulose; however, they are often inhibited by glucose. Previous studies demonstrated that glucose-6-phosphate (G6P) is a positive allosteric modulator of β-glucosidase A, improving enzymatic efficiency, providing thermoresistance, and imparting glucose tolerance. However, the precise molecular details of G6P-β-glucosidase A interactions have not yet been described so far. We investigated the molecular details of G6P binding into β-glucosidase A through in silico docking using the site identification by ligand competitive saturation technology followed by site-directed mutagenesis studies, from which an allosteric binding site for G6P was identified. In addition, a mechanistic shift toward the transglycosylation reaction as opposed to hydrolysis was observed in the presence of G6P, suggesting a new role of G6P allosteric modulation of the catalytic activity of β-glucosidase A.

DOI10.1021/acs.jcim.0c01450
Alternate JournalJ Chem Inf Model
PubMed ID33819021