Caenorhabditis elegans S-adenosylmethionine decarboxylase is highly stimulated by putrescine but exhibits a low specificity for activator binding.
S-Adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme of the polyamine synthetic pathway providing decarboxylated S-adenosylmethionine for the formation of spermidine and spermine, respectively. The catalytic activity of the AdoMetDC from the free-living nematode Caenorhabditis elegans highly depends on the presence of an activator molecule. Putrescine, a well-known stimulator of mammalian AdoMetDC activity, enhances the catalytic activity of the nematode enzyme 350-fold. Putrescine stimulation is discussed as a regulatory mechanism to relate putrescine abundance with the synthesis of spermidine and spermine. In contrast to any other known AdoMetDC, spermidine and spermine also represent significant activators of the nematode enzyme. However, the biological significance of the observed stimulation by these higher polyamines is unclear. Although C. elegans AdoMetDC exhibits a low specificity toward activator molecules, the amino acid residues that were shown to be involved in putrescine binding of the human enzyme are conserved in the nematode enzyme. Exchanging these residues by site-directed mutagenesis indicates that at least three residues, Thr192, Glu194 and Glu274, most likely contribute to activator binding in the C. elegans AdoMetDC. Interestingly, the mutant Glu194Gln exhibits a 100-fold enhanced basal activity in the absence of any stimulator, suggesting that this mutant protein mimics the conformational change usually induced by activator molecules. Furthermore, site-directed mutagenesis revealed that at least Glu33, Ser83, Arg91 and Lys95 are involved in posttranslational processing of C. elegans AdoMetDC.
Ndjonka
Dieudonne
D
Department of Biochemical Parasitology, Bernhard Nocht Institute for Tropical Medicine, Bernhard-Nocht-Str. 74, D-20359 Hamburg, Germany.
Da'dara
Akram
A
Walter
Rolf D
RD
Lüersen
Kai
K
D012437:Adenosylmethionine Decarboxylase / Q000096:biosynthesis* / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000378:metabolism*; D002384:Catalysis; D017124:Conserved Sequence; D020536:Enzyme Activators / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010957:Plasmids / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000235:genetics; D011700:Putrescine / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D013095:Spermidine / Q000494:pharmacology; D013096:Spermine / Q000494:pharmacology; D013268:Stimulation, Chemical; D013379:Substrate Specificity
D020536:Enzyme Activators; D011994:Recombinant Proteins; D013096:Spermine; D012437:Adenosylmethionine Decarboxylase; D013095:Spermidine; D011700:Putrescine