Phylogenetic diversity and the structural basis of substrate specificity in the β/α-barrel fold basic amino acid decarboxylases

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The β/α-barrel fold type basic amino acid decarboxylases include eukaryotic ornithine decarboxylases (ODC) and bacterial and plant enzymes with activity on L-arginine and meso-diaminopimelate. These enzymes catalyze essential steps in polyamine and lysine biosynthesis. Phylogenetic analysis suggests that diverse bacterial species also contain ODC-like enzymes from this fold type. However, in comparison with the eukaryotic ODCs, amino acid differences were identified in the sequence of the 310-helix that forms a key specificity element in the active site, suggesting they might function on novel substrates. Putative decarboxylases from a phylogenetically diverse range of bacteria were characterized to determine their substrate preference. Enzymes from species within Methanosarcina, Pseudomonas, Bartonella, Nitrosomonas, Thermotoga, and Aquifex showed a strong preference for L-ornithine, whereas the enzyme from Vibrio vulnificus (VvL/ODC) had dual specificity functioning well on both L-ornithine and L-lysine. The x-ray structure of VvL/ODC was solved in the presence of the reaction products putrescine and cadaverine to 1.7 and 2.15 Å, respectively. The overall structure is similar to eukaryotic ODC; however, reorientation of the 3 10-helix enlarging the substrate binding pocket allows L-lysine to be accommodated. The structure of the putrescine-bound enzyme suggests that a bridging water molecule between the shorter L-ornithine and key active site residues provides the structural basis for VvL/ODC to also function on this substrate. Our data demonstrate that there is greater structural and functional diversity in bacterial polyamine biosynthetic decarboxylases than previously suspected.

Original languageEnglish (US)
Pages (from-to)27115-27125
Number of pages11
JournalJournal of Biological Chemistry
Issue number37
StatePublished - Sep 14 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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