title: Structures of Saccharomyces cerevisiae D-arabinose dehydrogenase Ara1 and its complex with NADPH: implications for cofactor-assisted substrate recognition.
abstract: The primary role of yeast Ara1, previously mis-annotated as a D-arabinose dehydrogenase, is to catalyze the reduction of a variety of toxic α,β-dicarbonyl compounds using NADPH as a cofactor at physiological pH levels. Here, crystal structures of Ara1 in apo and NADPH-complexed forms are presented at 2.10 and 2.00 Å resolution, respectively. Ara1 exists as a homodimer, each subunit of which adopts an (α/β)8-barrel structure and has a highly conserved cofactor-binding pocket. Structural comparison revealed that induced fit upon NADPH binding yielded an intact active-site pocket that recognizes the substrate. Moreover, the crystal structures combined with computational simulation defined an open substrate-binding site to accommodate various substrates that possess a dicarbonyl group.
authors.affiliation: College of Life and Environment Science, Huangshan University, Huangshan, Anhui 245041, People's Republic of China.
authors.forename: Xiao-Qian
authors.initials: XQ
authors.lastname: Hu
authors.forename: Peng-Chao
authors.initials: PC
authors.lastname: Guo
authors.forename: Jin-Di
authors.initials: JD
authors.lastname: Ma
authors.forename: Wei-Fang
authors.initials: WF
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D055162:Biocatalysis; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009249:NADP / Q000378:metabolism*; D050837:Oxidoreductases Acting on Aldehyde or Oxo Group Donors / Q000737:chemistry* / Q000378:metabolism*; D055503:Protein Multimerization; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D013379:Substrate Specificity; D013401:Sugar Alcohol Dehydrogenases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: C000588781:Ara1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D009249:NADP; D013401:Sugar Alcohol Dehydrogenases; C028590:D-arabinose dehydrogenase; D050837:Oxidoreductases Acting on Aldehyde or Oxo Group Donors
keywords: Ara1; Saccharomyces cerevisiae; aldo–keto reductases; induced fit; substrate-binding pocket