title: Structure of the putative dihydroorotate dehydrogenase from Streptococcus mutans.
abstract: Streptococcus mutans is one of the pathogenic species involved in dental caries, especially in the initiation and development stages. Here, the crystal structure of SMU.595, a putative dihydroorotate dehydrogenase (DHOD) from S. mutans, is reported at 2.4 Å resolution. DHOD is a flavin mononucleotide-containing enzyme which catalyzes the oxidation of L-dihydroorotate to orotate, which is the fourth step and the only redox reaction in the de novo biosynthesis of pyrimidine nucleotides. The reductive lysine-methylation procedure was applied in order to improve the diffraction qualities of the crystals. Analysis of the S. mutans DHOD crystal structure shows that this enzyme is a class 1A DHOD and also suggests potential sites that could be exploited for the design of highly specific inhibitors using the structure-based chemotherapeutic design technique.
authors.affiliation: Department of Genetics, School of Life Science, Fudan University, Shanghai, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Zeng Qiang
authors.initials: ZQ
authors.lastname: Gao
authors.forename: Chao Pei
authors.initials: CP
authors.lastname: Liu
authors.forename: Jian Hua
authors.initials: JH
authors.lastname: Xu
authors.forename: Lan Fen
authors.initials: LF
authors.lastname: Li
authors.forename: Chao Neng
authors.initials: CN
authors.lastname: Ji
authors.forename: Xiao Dong
authors.initials: XD
authors.lastname: Su
authors.forename: Yu Hui
authors.initials: YH
authors.lastname: Dong
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D002384:Catalysis; D017124:Conserved Sequence; D018360:Crystallography, X-Ray / Q000379:methods; D003731:Dental Caries / Q000382:microbiology; D000090722:Dihydroorotate Dehydrogenase; D019281:Dimerization; D004926:Escherichia coli / Q000235:genetics; D005486:Flavin Mononucleotide / Q000737:chemistry / Q000378:metabolism; D006639:Histidine / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009963:Orotic Acid / Q000737:chemistry; D010084:Oxidation-Reduction; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary / Q000235:genetics; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D011743:Pyrimidines / Q000096:biosynthesis / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013295:Streptococcus mutans / Q000201:enzymology*; D013379:Substrate Specificity; D014961:X-Ray Diffraction
chemical_list: D000090722:Dihydroorotate Dehydrogenase; D021122:Protein Subunits; D011743:Pyrimidines; D011994:Recombinant Proteins; D006639:Histidine; D009963:Orotic Acid; D005486:Flavin Mononucleotide; D044925:Oxidoreductases Acting on CH-CH Group Donors; D008239:Lysine