title: Structural insights into the production of 3-hydroxypropionic acid by aldehyde dehydrogenase from Azospirillum brasilense.
abstract: 3-Hydroxypropionic acid (3-HP) is an important platform chemical to be converted to acrylic acid and acrylamide. Aldehyde dehydrogenase (ALDH), an enzyme that catalyzes the reaction of 3-hydroxypropionaldehyde (3-HPA) to 3-HP, determines 3-HP production rate during the conversion of glycerol to 3-HP. To elucidate molecular mechanism of 3-HP production, we determined the first crystal structure of a 3-HP producing ALDH, α-ketoglutarate-semialdehyde dehydrogenase from Azospirillum basilensis (AbKGSADH), in its apo-form and in complex with NAD+. Although showing an overall structure similar to other ALDHs, the AbKGSADH enzyme had an optimal substrate binding site for accepting 3-HPA as a substrate. Molecular docking simulation of 3-HPA into the AbKGSADH structure revealed that the residues Asn159, Gln160 and Arg163 stabilize the aldehyde- and the hydroxyl-groups of 3-HPA through hydrogen bonds, and several hydrophobic residues, such as Phe156, Val286, Ile288, and Phe450, provide the optimal size and shape for 3-HPA binding. We also compared AbKGSADH with other reported 3-HP producing ALDHs for the crucial amino acid residues for enzyme catalysis and substrate binding, which provides structural implications on how these enzymes utilize 3-HPA as a substrate.
authors.affiliation: School of Life Sciences, KNU Creative BioResearch Group, Kyungpook National University, Daehak-ro 80, Buk-ku, Daegu 702-701, Korea.
authors.forename: Hyeoncheol Francis
authors.initials: HF
authors.lastname: Son
authors.affiliation: School of Energy and Chemical Engineering, Ulsan national Institute of Science and Technology (UNIST), Ulsan 44919, Korea.
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 16499, Korea.
authors.forename: Tae Hyeon
authors.initials: TH
authors.lastname: Yoo
authors.affiliation: Department of Chemical Engineering and School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-gu, Pohang, Gyeongbuk 37673, Korea.
authors.forename: Gyoo Yeol
authors.initials: GY
authors.lastname: Jung
authors.affiliation: School of Life Sciences, KNU Creative BioResearch Group, Kyungpook National University, Daehak-ro 80, Buk-ku, Daegu 702-701, Korea.
authors.forename: Kyung-Jin
authors.initials: KJ
authors.lastname: Kim
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000737:chemistry* / Q000378:metabolism*; D000595:Amino Acid Sequence; D015806:Azospirillum brasilense / Q000201:enzymology*; D001665:Binding Sites; D055162:Biocatalysis; D019344:Lactic Acid / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000737:chemistry; D062105:Molecular Docking Simulation; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D055672:Static Electricity; D013379:Substrate Specificity
chemical_list: D009243:NAD; D019344:Lactic Acid; D009249:NADP; C031601:hydracrylic acid; D000444:Aldehyde Dehydrogenase