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 Pegg, Alexei Savchenko

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

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
Volume9
Issue number1
DOIs
StatePublished - Jan 1 2002

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Spermidine Synthase
Crystal structure
Polyamines
Thermotoga maritima
Oligomerization
Spermidine
Biosynthesis
Substrates
Enzymes
Catalytic Domain
Bacteria
Monomers
Binding Sites

All Science Journal Classification (ASJC) codes

  • Structural Biology
  • Biochemistry
  • Genetics

Cite this

Korolev, S., Ikeguchi, Y., Skarina, T., Beasley, S., Arrowsmith, C., Edwards, A., ... Savchenko, A. (2002). The crystal structure of spermidine synthase with a multisubstrate adduct inhibitor. Nature Structural Biology, 9(1), 27-31. https://doi.org/10.1038/nsb737
Korolev, Sergey ; Ikeguchi, Yoshihiko ; Skarina, Tatiana ; Beasley, Steven ; Arrowsmith, Cheryl ; Edwards, Aled ; Joachimiak, Andrzej ; Pegg, Anthony ; Savchenko, Alexei. / The crystal structure of spermidine synthase with a multisubstrate adduct inhibitor. In: Nature Structural Biology. 2002 ; Vol. 9, No. 1. pp. 27-31.
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Korolev, S, Ikeguchi, Y, Skarina, T, Beasley, S, Arrowsmith, C, Edwards, A, Joachimiak, A, Pegg, A & Savchenko, A 2002, 'The crystal structure of spermidine synthase with a multisubstrate adduct inhibitor', Nature Structural Biology, vol. 9, no. 1, pp. 27-31. https://doi.org/10.1038/nsb737

The crystal structure of spermidine synthase with a multisubstrate adduct inhibitor. / Korolev, Sergey; Ikeguchi, Yoshihiko; Skarina, Tatiana; Beasley, Steven; Arrowsmith, Cheryl; Edwards, Aled; Joachimiak, Andrzej; Pegg, Anthony; Savchenko, Alexei.

In: Nature Structural Biology, Vol. 9, No. 1, 01.01.2002, p. 27-31.

Research output: Contribution to journalArticle

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Korolev S, Ikeguchi Y, Skarina T, Beasley S, Arrowsmith C, Edwards A et al. The crystal structure of spermidine synthase with a multisubstrate adduct inhibitor. Nature Structural Biology. 2002 Jan 1;9(1):27-31. https://doi.org/10.1038/nsb737