Recurrent emergence of catalytically inactive ornithine decarboxylase homologous forms that likely have regulatory function.
Ornithine decarboxylase (ODC) catalyzes the first and rate limiting step in the biosynthesis of polyamines in most eukaryotes. Because polyamines have pleiotropic and often dramatic effects on cellular processes at both high and low concentrations, ODC expression is tightly controlled. ODC is regulated by a family of polyamine-induced proteins, antizymes, which bind to, and inactivate it. In mammals, and apparently most vertebrates, antizymes are in turn antagonized by proteins called antizyme inhibitors. Antizyme inhibitors are homologs of ODC that have lost their decarboxylation activity but have retained their ability to bind antizyme, in most cases even more tightly than ODC. We present a phylogenetic analysis of over 200 eukaryotic homologs of ODC and evaluate their potential to be either true ODCs or catalytically inactive proteins that might be analogs of the previously identified antizyme inhibitors. This analysis yielded several orthologous groups of putative novel antizyme inhibitors each apparently arising independently. In the process we also identify previously unrecognized ODC paralogs in several evolutionary branches, including a previously unrecognized ODC paralog in mammals, and we evaluate their biochemical potential based on their pattern of amino acid conservation.
Ivanov
Ivaylo P
IP
BioSciences Institute, University College Cork, Ireland.
Firth
Andrew E
AE
Atkins
John F
JF
D000818:Animals; D002384:Catalysis; D004789:Enzyme Activation / Q000235:genetics / Q000502:physiology; D019143:Evolution, Molecular; D006801:Humans; D007448:Invertebrates / Q000201:enzymology / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009955:Ornithine Decarboxylase / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D010802:Phylogeny; D011506:Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D012008:Recurrence; D017385:Sequence Homology; D013329:Structure-Activity Relationship; D014714:Vertebrates / Q000235:genetics
D007527:Isoenzymes; D011506:Proteins; C031017:ornithine decarboxylase antizyme; D009955:Ornithine Decarboxylase