Dataset for "Control of Substrate Conformation by Hydrogen Bonding in a Retaining β-Endoglycosidase"

This data set contains files related to the article "Control of Substrate Conformation by Hydrogen Bonding in a Retaining β-Endoglycosidase" by Alba Nin-Hill, Albert Ardèvol, Xevi Biarnés, Antoni Planas and Carme Rovira. ABSTRACT Bacterial β-glycosidases are hydrolytic enzymes that depolymerize polysaccharides such as β-cellulose, β-glucans and β-xylans from different sources are used in a myriad of biomedical and industrial applications. It has been shown that a conformational change of the substrate, from a relaxed 4C1 conformation to a distorted 1S3/1,4B conformation of the reactive sugar, is necessary for catalysis. However, the molecular determinants that stabilize the substrate's distortion are poorly understood. Here we use quantum mechanics/molecular mechanics (QM/MM)-based molecular dynamics methods to assess the impact of the interaction between the reactive sugar, i.e. the one at subsite -1, and the catalytic nucleophile (a glutamate) on substrate conformation. We show that the hydrogen bond involving the C2 exocyclic group and the nucleophile controls substrate conformation: its presence preserves sugar distortion, whereas its absence (e.g. in an enzyme mutant) knocks it out. We also show that 2-deoxy-2-fluoro derivatives, widely used to trap the reaction intermediates by X-ray crystallography, reproduce the conformation of the hydrolysable substrate at the experimental conditions. These results highlight the importance of the 2-OH···nucleophile interaction in substrate recognition and catalysis in endo-glycosidases and can inform mutational campaigns aimed to search for more efficient enzymes. DESCRIPTION OF THE DATASET The data is compressed in a .rar file in where we would find the following folders: Model1_WT Model2_2deoxy2F_lowpH Model3_2deoxy2F_neutralpH Model4_Glu105Gln_lowpH Model5_Glu105Gln_neutralpH Model6_Glu105Asp_neutralpH Model7_Glu105Ala_lowpH Model8_Glu105Ile_lowpH Model8_Glu105Ile_lowpH Model10_Glu105Ile_neutralpH scripts Each folder contains the first frame of the production phase of the QM/MM MD simulations in a .pdb format and the representative structures of the whole simulation obtained by clustering in a .nc format. In the scripts folder we can find the scripts used to calculate and analyze the QM/MM MD simulations and a README.txt file with their proper descriptions. More data can be made available upon reasonable request.