Disease relevance of SPE3

• Key regions in the active site, which are very highly conserved, were identified by structural studies with spermidine synthase from Thermotoga maritima bound to S-adenosyl-1,8-diamino-3-thiooctane, a multisubstrate analog inhibitor [1].

High impact information on SPE3

• The lower spermidine level in the meu1Delta cells probably results from an inhibition of spermidine synthase by the methylthioadenosine that presumably accumulates in these mutants [2].
• We were able to show this specificity by using a spe3Delta fms1Delta mutant that lacked both spermidine synthase and the FMS1-encoded amine oxidase that oxidizes spermine to spermidine [3].
• We cloned the gene complementing the frd3-1 phenotype and found that it was identical to SPE3, which encodes spermidine synthase [4].
• Addition of spermidine to the medium partially restored repression to spe3 cells, indicating that spermidine may play a role in vivo as a modulator of gene expression [4].
• 4. 2. S-Adenosylmethionine decarboxylase activity was completely separated from spermidine synthase activity [5'-deoxyadenosyl-(5'),3-aminopropyl-(1),methylsulphonium-salt-putrescine 3-aminopropyltransferase, EC 2.5.1.16] during the purification procedure [5].

Biological context of SPE3

• Consistent with the importance of saccharopine dehydrogenase and spermidine synthase in vitro, spe3-lys9 mutants were avirulent and unable to survive in vivo and both functions individually contributed to virulence [6].
• However, the rest of the pathway including ornithine decarboxylase and spermidine synthase was probably inherited from bacterial genes present in the original host cell, common ancestor of plants and animals, that acquired the cyanobacterial endosymbiont [7].
• The Saccharomyces cerevisiae SPE3 gene, coding for spermidine synthase, was cloned, sequenced, and localized on the right arm of chromosome XVI [8].
• Spermidine synthase is an essential gene in eukaryotes and is very widely distributed [1].
• The higher homologues of cadaverine, aminopropylcadaverine (APC) and N,N-bis(3-aminopropyl)cadaverine (3APC) were formed by a wild-type strain of Saccharomyces cerevisiae, and by two mutant strains, spe 3-1 and spe 4-1, exhibiting point mutations in the genes for spermidine synthase and spermine synthase, respectively [9].

Associations of SPE3 with chemical compounds

• To investigate the effect of total loss of the SPE3 gene, we constructed a null mutant of this gene, spe3delta, which has no spermidine synthase activity and has an absolute requirement for spermidine or spermine for the growth [8].
• SPE3-LYS9 mRNA levels showed little evidence of being influenced by exogenous spermidine or lysine or starvation for spermidine or lysine; thus, any regulation is likely to be posttranscriptional [6].
• Thus, SPE3-LYS9 encodes functional spermidine synthase and saccharopine dehydrogenase gene products [6].
• In contrast to Saccharomyces cerevisiae spe3 mutants, the polyamine auxotrophy of C. neoformans spe3-LYS9 mutants was not satisfied by spermine [6].

Other interactions of SPE3

• Novel chimeric spermidine synthase-saccharopine dehydrogenase gene (SPE3-LYS9) in the human pathogen Cryptococcus neoformans [6].
• The best known aminopropyltransferases are spermidine synthase and spermine synthase but other members of this family including an N(1)-aminopropylagmatine synthase have been characterized [1].

References