title: The crystal structure of spermidine synthase with a multisubstrate adduct inhibitor.
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 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.
authors.affiliation: Biosciences Division and Structural Biology Center, Argonne National Laboratory, 9700 South Cass Ave., Bldg. 202, Argonne, Illinois 60439, USA.
authors.forename: Sergey
authors.initials: S
authors.lastname: Korolev
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Ikeguchi
authors.forename: Tatiana
authors.initials: T
authors.lastname: Skarina
authors.forename: Steven
authors.initials: S
authors.lastname: Beasley
authors.forename: Cheryl
authors.initials: C
authors.lastname: Arrowsmith
authors.forename: Aled
authors.initials: A
authors.lastname: Edwards
authors.forename: Andrzej
authors.initials: A
authors.lastname: Joachimiak
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Pegg
authors.forename: Alexei
authors.initials: A
authors.lastname: Savchenko
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D001051:Apoenzymes / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D008970:Molecular Weight; D011073:Polyamines / Q000378:metabolism; D011487:Protein Conformation; D016415:Sequence Alignment; D011436:Spermidine Synthase / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D020124:Thermotoga maritima / Q000201:enzymology*
chemical_list: D001051:Apoenzymes; D004791:Enzyme Inhibitors; D011073:Polyamines; C027548:S-adenosyl-3-thio-1,8-diaminooctane; D011436:Spermidine Synthase; D000241:Adenosine