The crystal structure of spermidine synthase with a multisubstrate adduct inhibitor

Sergey Korolev, Yoshihiko Ikeguchi, Tatiana Skarina, Steven Beasley, Cheryl Arrowsmith, Aled Edwards, Andrzej Joachimiak, Anthony E. Pegg, Alexei Savchenko

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128 Scopus citations


Polyamines are essential in all branches of life. Spermidine synthase (putrescine aminopropyltransferase, PAPT) catalyzes the biosynthesis of spermidine, a ubiquitous polyamine. The crystal structure of the PAPT from Thermotoga maritima (TmPAPT) has been solved to 1.5 Å resolution in the presence and absence of AdoDATO (S-adenosyl-1,8-diamino-3-thiooctane), a compound containing both substrate and product moieties. This, the first structure of an aminopropyltransferase, reveals deep cavities for binding substrate and cofactor, and a loop that envelops the active site. The AdoDATO binding site is lined with residues conserved in PAPT enzymes from bacteria to humans, suggesting a universal catalytic mechanism. Other conserved residues act sterically to provide a structural basis for polyamine specificity. The enzyme is tetrameric; each monomer consists of a C-terminal domain with a Rossmann-like fold and an N-terminal β-stranded domain. The tetramer is assembled using a novel barrel-type oligomerization motif.

Original languageEnglish (US)
Pages (from-to)27-31
Number of pages5
JournalNature Structural Biology
Issue number1
StatePublished - 2002

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry
  • Genetics


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