flavin-mononucleotide and Dental-Caries

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.

Topics: Amino Acid Sequence; Binding Sites; Catalysis; Conserved Sequence; Crystallography, X-Ray; Dental Caries; Dihydroorotate Dehydrogenase; Dimerization; Escherichia coli; Flavin Mononucleotide; Histidine; Humans; Hydrophobic and Hydrophilic Interactions; Lysine; Methylation; Models, Molecular; Molecular Sequence Data; Orotic Acid; Oxidation-Reduction; Oxidoreductases Acting on CH-CH Group Donors; Protein Conformation; Protein Folding; Protein Structure, Quaternary; Protein Structure, Secondary; Protein Subunits; Pyrimidines; Recombinant Proteins; Sequence Homology, Amino Acid; Streptococcus mutans; Substrate Specificity; X-Ray Diffraction