Structure of the putative dihydroorotate dehydrogenase from Streptococcus mutans

Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Feb 1;67(Pt 2):182-7. doi: 10.1107/S1744309110048414. Epub 2011 Jan 21.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Dihydroorotate Dehydrogenase
  • Protein Subunits
  • Pyrimidines
  • Recombinant Proteins
  • Histidine
  • Orotic Acid
  • Flavin Mononucleotide
  • Oxidoreductases Acting on CH-CH Group Donors
  • Lysine

Associated data

  • PDB/3OIX