The crystal structure of spermidine synthase with a multisubstrate adduct inhibitor

Nat Struct Biol. 2002 Jan;9(1):27-31. doi: 10.1038/nsb737.


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 A 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 beta-stranded domain. The tetramer is assembled using a novel barrel-type oligomerization motif.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / chemistry
  • Adenosine / metabolism
  • Amino Acid Sequence
  • Apoenzymes / antagonists & inhibitors
  • Apoenzymes / chemistry
  • Apoenzymes / metabolism
  • Binding Sites
  • Catalysis
  • Chromatography, High Pressure Liquid
  • Crystallography, X-Ray
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Molecular Weight
  • Polyamines / metabolism
  • Protein Conformation
  • Sequence Alignment
  • Spermidine Synthase / antagonists & inhibitors*
  • Spermidine Synthase / chemistry*
  • Structure-Activity Relationship
  • Substrate Specificity
  • Thermotoga maritima / enzymology*


  • Apoenzymes
  • Enzyme Inhibitors
  • Polyamines
  • S-adenosyl-3-thio-1,8-diaminooctane
  • Spermidine Synthase
  • Adenosine

Associated data

  • PDB/1INL
  • PDB/1JQ3