Structural Basis for Broad Substrate Selectivity of Alcohol Dehydrogenase YjgB from Escherichia coli

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 10; p. 2404
• Main Authors: Nguyen, Giang Thu, Kim, Yeon-Gil, Ahn, Jae-Woo, Chang, Jeong Ho
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21-05-2020; MDPI
• Subjects: Adenine; Alcohol; Alcohol dehydrogenase; Alcohol Dehydrogenase - chemistry; Alcohol Dehydrogenase - genetics; Alcohol Dehydrogenase - ultrastructure; Alcohol Oxidoreductases - chemistry; Alcohol Oxidoreductases - genetics; Alcohol Oxidoreductases - ultrastructure; Aldehyde dehydrogenase; Aldehydes; Aliphatic compounds; Aromatic compounds; Binding sites; Binding Sites - genetics; Biofuels; broad specificity; Catalytic Domain - genetics; Crystal structure; Crystallography, X-Ray; Dehydrogenase; Dehydrogenases; docking-simulation; E coli; Enzymes; Escherichia coli; Escherichia coli - enzymology; Escherichia coli - genetics; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - genetics; Escherichia coli Proteins - ultrastructure; hydrophobic pocket; Hydrophobicity; Isobutanol; Ligands; Metabolic Engineering; Metabolism; Models, Molecular; NADP; NADPH-diaphorase; Nicotinamide; Polyethylene glycol; Protein Conformation; Selectivity; Structural analysis; Substrate Specificity; Substrates; YjgB; Zinc; crystal structure; docking-simulation; hydrophobic pocket; aldehyde dehydrogenase; YjgB; broad specificity
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25102404

In metabolic engineering and synthetic biology fields, there have been efforts to produce variable bioalcohol fuels, such as isobutanol and 2-phenylethanol, in order to meet industrial demands. YjgB is an aldehyde dehydrogenase from Escherichia coli that shows nicotinamide adenine dinucleotide phosphate (NADP)-dependent broad selectivity for aldehyde derivatives with an aromatic ring or small aliphatic chain. This could contribute to the design of industrial synthetic pathways. We determined the crystal structures of YjgB for both its apo-form and NADP-complexed form at resolutions of 1.55 and 2.00 Å, respectively, in order to understand the mechanism of broad substrate selectivity. The hydrophobic pocket of the active site and the nicotinamide ring of NADP(H) are both involved in conferring its broad specificity toward aldehyde substrates. In addition, based on docking-simulation data, we inferred that π-π stacking between substrates and aromatic side chains might play a crucial role in recognizing substrates. Our structural analysis of YjgB might provide insights into establishing frameworks to understand its broad substrate specificity and develop engineered enzymes for industrial biofuel synthesis.