title: Crystal structure of a bifunctional deaminase and reductase from Bacillus subtilis involved in riboflavin biosynthesis.
abstract: Bacterial RibG is an attractive candidate for development of antimicrobial drugs because of its involvement in the riboflavin biosynthesis. The crystal structure of Bacillus subtilis RibG at 2.41-A resolution displayed a tetrameric ring-like structure with an extensive interface of approximately 2400 A(2)/monomer. The N-terminal deaminase domain belongs to the cytidine deaminase superfamily. A structure-based sequence alignment of a variety of nucleotide deaminases reveals not only the unique signatures in each family member for gene annotation but also putative substrate-interacting residues for RNA-editing deaminases. The strong structural conservation between the C-terminal reductase domain and the pharmaceutically important dihydrofolate reductase suggests that the two reductases involved in the riboflavin and folate biosyntheses evolved from a single ancestral gene. Together with the binding of the essential cofactors, zinc ion and NADPH, the structural comparison assists substrate modeling into the active-site cavities allowing identification of specific substrate recognition. Finally, the present structure reveals that the deaminase and the reductase are separate functional domains and that domain fusion is crucial for the enzyme activities through formation of a stable tetrameric structure.
authors.affiliation: Structural Biology Program, Institute of Biochemistry, and Faculty of Life Science, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Sheng-Chia
authors.initials: SC
authors.lastname: Chen
authors.forename: Yuan-Chih
authors.initials: YC
authors.lastname: Chang
authors.forename: Chao-Hsiung
authors.initials: CH
authors.lastname: Lin
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Shwu-Huey
authors.initials: SH
authors.lastname: Liaw
mesh_terms: D000595:Amino Acid Sequence; D001412:Bacillus subtilis / Q000737:chemistry / Q000201:enzymology*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007477:Ions; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009249:NADP / Q000737:chemistry; D009709:Nucleotide Deaminases / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012256:Riboflavin / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013237:Stereoisomerism; D013379:Substrate Specificity; D013401:Sugar Alcohol Dehydrogenases / Q000737:chemistry* / Q000378:metabolism; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; D007477:Ions; D009249:NADP; D013401:Sugar Alcohol Dehydrogenases; D013762:Tetrahydrofolate Dehydrogenase; C104886:RibG protein, Bacillus subtilis; D009709:Nucleotide Deaminases; D015032:Zinc; D012256:Riboflavin