The crystal structure of spermidine synthase with a multisubstrate adduct inhibitor.
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 Angstroms 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.
- Research Organization:
- Argonne National Lab. (ANL), Argonne, IL (United States)
- Sponsoring Organization:
- National Institutes of Health (NIH); USDOE Office of Science (SC); FOR
- DOE Contract Number:
- DE-AC02-06CH11357
- OSTI ID:
- 949508
- Report Number(s):
- ANL/BIO/JA-41621; TRN: US201012%%296
- Journal Information:
- Nature Struct. Biol., Vol. 9, Issue 1 ; Jan. 2002
- Country of Publication:
- United States
- Language:
- ENGLISH
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