title: Structural insights into cofactor recognition of yeast mitochondria 3-oxoacyl-ACP reductase OAR1.
abstract: 3-Oxoacyl-(acyl-carrier-protein) reductase (OAR1 or FabG, EC.1.1.1.100) is responsible for the first reductive step in fatty acid biosynthesis using Nicotinamide Adenine Dinucleotide Phosphate (NADPH) as a cofactor. Recent studies suggest there is a fatty acid synthetase II pathway that consists of a series of separate enzymes in yeast mitochondrion. Here, we present the crystal structure of the yeast mitochondria OAR1 (ymtOAR1) alone in apo-form at 2.60 Å and complexed with NADPH at 2.10 Å resolution. Unlike the reported tetrameric OARs, ymtOAR1 forms a homodimer due to the different fold. The enzyme generates conformational changes upon NADPH binding to the active site. Moreover, two different cofactor-binding patterns are observed from two forms of complex crystals, and structural analysis implies the adenine end of cofactor may recognize enzyme prior to nicotinaminde end. Additionally, biochemical studies suggest Arg14 is important for cofactor recognition of ymtOAR1.
authors.affiliation: Hefei National Laboratory for Physical Sciences at the Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: YuJie
authors.initials: Y
authors.lastname: Zhang
authors.forename: FangKun
authors.initials: F
authors.lastname: Ning
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.forename: MaiKun
authors.initials: M
authors.lastname: Teng
mesh_terms: D064431:3-Oxoacyl-(Acyl-Carrier-Protein) Reductase; D000429:Alcohol Oxidoreductases / Q000737:chemistry*; D000595:Amino Acid Sequence; D001051:Apoenzymes / Q000737:chemistry; D020134:Catalytic Domain; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D008958:Models, Molecular; D058977:Molecular Sequence Annotation; D009243:NAD / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D016415:Sequence Alignment; D013499:Surface Properties
chemical_list: D001051:Apoenzymes; D029701:Saccharomyces cerevisiae Proteins; D009243:NAD; D000429:Alcohol Oxidoreductases; D064431:3-Oxoacyl-(Acyl-Carrier-Protein) Reductase