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 language | English (US) |
|---|---|
| Pages (from-to) | 27-31 |
| Number of pages | 5 |
| Journal | Nature Structural Biology |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2002 |
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All Science Journal Classification (ASJC) codes
- Structural Biology
- Biochemistry
- Genetics
Cite this
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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 journal › Article
TY - JOUR
T1 - The crystal structure of spermidine synthase with a multisubstrate adduct inhibitor
AU - Korolev, Sergey
AU - Ikeguchi, Yoshihiko
AU - Skarina, Tatiana
AU - Beasley, Steven
AU - Arrowsmith, Cheryl
AU - Edwards, Aled
AU - Joachimiak, Andrzej
AU - Pegg, Anthony
AU - Savchenko, Alexei
PY - 2002/1/1
Y1 - 2002/1/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0036142291&partnerID=8YFLogxK
U2 - 10.1038/nsb737
DO - 10.1038/nsb737
M3 - Article
C2 - 11731804
AN - SCOPUS:0036142291
VL - 9
SP - 27
EP - 31
JO - Nature Structural and Molecular Biology
JF - Nature Structural and Molecular Biology
SN - 1545-9993
IS - 1
ER -