MODELING OF THE SPATIAL STRUCTURE OF EUKARYOTIC ORNITHINE DECARBOXYLASES

We used sequence and structural comparisons to determine the fold for eukaryotic ornithine decarboxylase, which we found is related to alani ne racemase. These enzymes have no detectable sequence identity with a ny protein of known structure, including three pyridoxal phosphate-uti lizing enzymes. Our studies suggest that the N-terminal domain af orni thine decarboxylase folds into a beta/alpha-barrel. Through the analys is of known barrel structures we developed a topographic model of the pyridoxal phosphate-binding domain of ornithine decarboxylase, which p redicts that the Schiff base lysine and a conserved glycine-rich seque nce both map to the C-termini of the beta-strands. Other residues in t his domain that are likely to have essential roles in catalysis, subst rate, and cofactor binding were also identified, suggesting that this model will be a suitable guide to mutagenic analysis of the enzyme mec hanism.