Phylogenetic Diversity and the Structural Basis of Substrate Specificity in the Beta/Alpha-barrel Fold Basic Amino Acid Decarboxylases.
From: Departments of Pharmacology and Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9041, USA.
The Journal of biological chemistry
- Publish Date: Sep 2007
- ISSN: 0021-9258
- Volume: 282
- Issue: 37
- Pages: 27115-25
- Medium: Print
- Language: English
- Citation (JAMA): Lee Jeongmi, Michael Anthony J, Martynowski Dariusz, et al. Phylogenetic Diversity and the Structural Basis of Substrate Specificity in the Beta/Alpha-barrel Fold Basic Amino Acid Decarboxylases.. J. Biol. Chem. Sep 2007;282:27115-25
Abstract
The beta/alpha-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 3(10)-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 2.15A, 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.
Mesh Headings (Keywords): Amino Acid Sequence, Bacteria, Eflornithine, Molecular Sequence Data, Ornithine Decarboxylase, Phylogeny, Protein Folding, Substrate Specificity
Check for Full Text / PubMed Unique Identifier (PMID): 17626020
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