Spermine synthase

Abstract

Spermine is present in many organisms including animals, plants, some fungi, some archaea, and some bacteria. It is synthesized by spermine synthase, a highly specific aminopropyltransferase. This review describes spermine synthase structure, genetics, and function. Structural and biochemical studies reveal that human spermine synthase is an obligate dimer. Each monomer contains a C-terminal domain where the active site is located, a central linking domain that also forms the lid of the catalytic domain, and an N-terminal domain that is structurally very similar to S-adenosylmethionine decarboxylase. Gyro mice, which have an X-chromosomal deletion including the spermine synthase (SMS) gene, lack all spermine and have a greatly reduced size, sterility, deafness, neurological abnormalities, and a tendency to sudden death. Mutations in the human SMS lead to a rise in spermidine and reduction of spermine causing Snyder-Robinson syndrome, an X-linked recessive condition characterized by mental retardation, skeletal defects, hypotonia, and movement disorders.

Fig. 1

Spermine synthase structure and function. a The dimeric structure of spermine synthase. The bound molecules of spermidine and MTA are shown in sphere representation with carbon atoms in gray. b A monomer of spermine synthase with the dimerization interface in magenta. c Comparison of structures of monomers of human spermine synthase (SpmSyn), human spermidine synthase (SpdSyn), and T. maritima AdoMetDC proenzyme. d The postulated reaction mechanism. The spermidine and dcAdoMet substrates are shown in black and the key protein residues in green. A red arrow indicates the proposed attack by the spermidine amino group on the methylene carbon of the aminopropyl group. This figure is derived (with permission) from Figs. 2 and 7 in [13]

Fig. 2

Neighbor-joining tree of amino acid sequences of diverse aminopropyltransferases. Trimming eliminated the extended N-terminal domain of metazoan spermine synthases and the saccharopine dehydrogenase C-terminal domain of Basidiomycota spermidine synthases. Alignment and neighbor-joining tree construction was performed as described [13]. Sequence names preceded by a red asterisk indicate aminopropyltransferase activities functionally confirmed. GeneBank protein sequence accession numbers are given in parentheses, numbers preceded by JGI indicate sequences from the Department of Energy Joint Genome Institute Genome Portal (http://genome.jgi-psf.org/) and the Cyanidioschyzon merolae sequences are from the corresponding Cyanidioschyzon merolae genome project (http://merolae.biol.s.u-tokyo.ac.jp/blast/blast.html). Figures represent percent value for 1,000 bootstrap replicates. The alignment upon which the tree is based is provided as an on-line supplementary figure