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 E.
AU - Savchenko, Alexei
N1 - Funding Information:
We wish to thank all members of the SBC at ANL for their help in conducting experiments and L. Keller for help in preparation of this manuscript. This work was supported by the National Institutes of Health; the U.S. Department of Energy, Office of Biological and Environmental Research; the Ontario Research and Development Challenge Fund; and National Institutes of Health. A.M.E. and C.H.A. are CIHR Investigators. The submitted manuscript has been created by the University of Chicago as Operator of Argonne National Laboratory (‘Argonne’) under contract with the U.S. Department of Energy. The U.S. Government retains for itself, and others acting on its behalf, a paid-up, nonexclusive, irrevocable worldwide license in said article to reproduce, prepare derivative works, distribute copies to the public, and perform publicly and display publicly, by or on behalf of the Government.
PY - 2002
Y1 - 2002
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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U2 - 10.1038/nsb737
DO - 10.1038/nsb737
M3 - Article
C2 - 11731804
AN - SCOPUS:0036142291
VL - 9
SP - 27
EP - 31
JO - Nature Structural Biology
JF - Nature Structural Biology
SN - 1545-9993
IS - 1
ER -