PROCESSING OF MAMMALIAN AND PLANT S-ADENOSYLMETHIONINE DECARBOXYLASE PROENZYMES

S-Adenosylmethionine decarboxylase (AdoMetDC) is a pyruvoyl enzyme, an d the pyruvate is formed in an intramolecular reaction that cleaves a proenzyme precursor and converts a serine residue into pyruvate, The w ild type potato AdoMetDC proenzyme processed much faster than the huma n proenzyme and did not require putrescine for an optimal rate of proc essing despite the presence of three acidic residues (equivalent to Gl u(11), Glu(178), and Glu(256)) that were demonstrated in previous stud ies to be required for the putrescine activation of human AdoMetDC pro enzyme processing (Stanley, B. A., Shantz, L. M., and Pegg, A. E. (199 4) J. Biol, Chem. 269, 7901-7907), A fourth residue that is also neede d for the putrescine stimulation of human AdoMetDC proenzyme processin g was identified in the present studies, and this residue (Asp(174)) i s not present in the potato sequence, The site of potato AdoMetDC proe nzyme processing was found to be Ser(73) in the conserved sequence, YV LSE (S) under bar S, which is the equivalent of Ser(68) in the human s equence, Replacement of the serine precursor with threonine or cystein e by site-directed mutagenesis in either the potato or the human AdoMe tDC proenzyme did not prevent processing but caused a significant redu ction in the rate, Although the COOH-terminal regions of the known euk aryotic AdoMetDCs are not conserved, only relatively small truncations of 8 residues from the human protein and 25 residues from the potato proenzyme were compatible with processing. The maximally truncated pro teins show no similarity in COOH-terminal amino acid sequence but each contained 46 amino acid residues after the last conserved sequence, s uggesting that the length of this section of the protein is essential for maintaining the proenzyme conformation needed for autocatalytic pr ocessing.