Evolutionary links as revealed by the structure of Thermotoga maritima S-adenosylmethionine decarboxylase.

Publication Type:

Journal Article


J Biol Chem, Volume 279, Issue 32, p.33837-46 (2004)


Adenosylmethionine Decarboxylase, Amino Acid Sequence, Binding Sites, Catalysis, Conserved Sequence, Crystallization, Crystallography, X-Ray, Dimerization, Enzyme Precursors, Escherichia coli, Evolution, Molecular, Gene Expression, Humans, Models, Molecular, Molecular Sequence Data, Molecular Structure, Mutagenesis, Site-Directed, Polymerase Chain Reaction, Protein Folding, Solanum tuberosum, Thermotoga maritima


<p>S-adenosylmethionine decarboxylase (AdoMetDC) is a critical regulatory enzyme of the polyamine biosynthetic pathway and belongs to a small class of pyruvoyl-dependent amino acid decarboxylases. Structural elucidation of the prokaryotic AdoMetDC is of substantial interest in order to determine the relationship between the eukaryotic and prokaryotic forms of the enzyme. Although both forms utilize pyruvoyl groups, there is no detectable sequence similarity except at the site of pyruvoyl group formation. The x-ray structure of the Thermatoga maritima AdoMetDC proenzyme reveals a dimeric protein fold that is remarkably similar to the eukaryotic AdoMetDC protomer, suggesting an evolutionary link between the two forms of the enzyme. Three key active site residues (Ser55, His68, and Cys83) involved in substrate binding, catalysis or proenzyme processing that were identified in the human and potato AdoMet-DCs are structurally conserved in the T. maritima AdoMetDC despite very limited primary sequence identity. The role of Ser55, His68, and Cys83 in the self-processing reaction was investigated through site-directed mutagenesis. A homology model for the Escherichia coli AdoMetDC was generated based on the structures of the T. maritima and human AdoMetDCs.</p>