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Information on EC 2.3.1.57 - diamine N-acetyltransferase
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EC Tree
2.3.1.57 diamine N-acetyltransferaseIUBMB Comments
Acts on propane-1,3-diamine, pentane-1,5-diamine, putrescine, spermidine (forming N1- and N8-acetylspermidine), spermine, N1-acetylspermidine and N8-acetylspermidine.
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Word Map
- 2.3.1.57
-
polyamine
- ornithine
- s-adenosylmethionine
- n1-acetylspermidine
- alpha-difluoromethylornithine
-
denspm
- n1,n11-diethylnorspermine
- n1,n12-bisethylspermine
-
mesenteroides
-
leuconostoc
-
reuteri
- glucans
-
glucosylated
- glucansucrases
- pao
- analysis
- dextransucrase
- pharmacology
-
antizyme
-
bisguanylhydrazone
-
superinduction
-
n1-acetylation
- medicine
- drug development
- adometdc
-
malme-3m
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
spermidine/spermine n1-acetyltransferase, spermidine n1-acetyltransferase, ssat1, ssat2, spermidine acetyltransferase, spermidine/spermine-n1-acetyltransferase, spermidine n-acetyltransferase, ssat-1, n1ssat, n1-sat, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
acetyl-coenzyme A-1,4-diaminobutane N-acetyltransferase
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acetyltransferase, putrescine
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-
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diamine acetyltransferase
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N1-SAT
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N1SSAT
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PaiA
putrescine (diamine)-acetylating enzyme
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putrescine acetylase
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putrescine acetyltransferase
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putrescine N-acetyltransferase
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SAT1
SpeG
spermidine acetyltransferase
spermidine N-acetyltransferase
spermidine N1-acetyltransferase
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spermidine/spermine N1-acetyltransferase
spermidine/spermine N1-acetyltransferase 1
spermidine/spermine-N1-acetyltransferase
SSAT
SSAT1
VCA0947
additional information
spermidine acetyltransferase
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-
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spermidine/spermine N1-acetyltransferase
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spermidine/spermine N1-acetyltransferase
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spermidine/spermine N1-acetyltransferase 1
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SSAT
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SSAT
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-
additional information
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SSAT is a member of the GCN5-related N-acetyltransferase, GNAT, family
additional information
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SSAT belongs to the GCN5-related N-acetyltransferase, GNAT, superfamily of acetyltransferases
additional information
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SSAT is a member of the GCN5-related N-acetyltransferase, GNAT, family
additional information
-
SSAT is a member of the GCN5-related N-acetyltransferase, GNAT, family
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
acetyl-CoA + an alkane-alpha,omega-diamine = CoA + an N-acetyldiamine
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-
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acetyl-CoA + an alkane-alpha,omega-diamine = CoA + an N-acetyldiamine
sequential mechanism
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acetyl-CoA + an alkane-alpha,omega-diamine = CoA + an N-acetyldiamine
sequential mechanism
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acetyl-CoA + an alkane-alpha,omega-diamine = CoA + an N-acetyldiamine
sequential mechanism
Trichosporon melibiosaceum
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acetyl-CoA + an alkane-alpha,omega-diamine = CoA + an N-acetyldiamine
the acetylation proceeds by Bi-Bi mechanism
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acetyl-CoA + an alkane-alpha,omega-diamine = CoA + an N-acetyldiamine
Glu92 functions as a catalytic base to drive an otherwise unfavorable deprotonation step at physiological pH. Spermine and the enzyme and form a proton wire between the side chain of Glu92 and the N1 amine of spermine, a single water molecule forms hydrogen bonds with the side chains of Glu92, Asp93, and the N4 amine of spermine, substrate binding structure, overview
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acetyl-CoA + an alkane-alpha,omega-diamine = CoA + an N-acetyldiamine
sequential mechanism
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acetyl-CoA + an alkane-alpha,omega-diamine = CoA + an N-acetyldiamine
sequential mechanism
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acetyl-CoA + an alkane-alpha,omega-diamine = CoA + an N-acetyldiamine
sequential mechanism
Trichosporon melibiosaceum CBS 6087
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Acyl group transfer
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PATHWAY SOURCE
PATHWAYS
BRENDA
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SYSTEMATIC NAME
IUBMB Comments
acetyl-CoA:alkane-alpha,omega-diamine N-acetyltransferase
Acts on propane-1,3-diamine, pentane-1,5-diamine, putrescine, spermidine (forming N1- and N8-acetylspermidine), spermine, N1-acetylspermidine and N8-acetylspermidine.
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CAS REGISTRY NUMBER
COMMENTARY
54596-36-0
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + (S)-2-[(3-aminopropyl)amino]ethylphosphoric acid
CoA + N-acetyl-(S)-2-[(3-aminopropyl)amino]ethylphosphoric acid
-
WR-2721, about 10% of the rate with spermidine
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-
?
acetyl-CoA + (S)-2-[(3-aminopropyl)amino]propylphosphoric acid
CoA + N-acetyl-(S)-2-[(3-aminopropyl)amino]propylphosphoric acid
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WR-44923, about 10% of the rate with spermidine
-
-
?
acetyl-CoA + 1,7-diaminoheptane
CoA + N1-acetyl-1,7-diaminoheptane
-
-
-
-
?
acetyl-CoA + 15-deoxyspergualin
?
-
antitumor and immunosuppressive agent 15-deoxyspergualin, about 18% of the rate with spermidine
-
-
?
acetyl-CoA + 2-[(aminopropyl)amino]ethanethiol
CoA + N-acetyl-2-[(aminopropyl)amino]ethanethiol
-
radioprotective drug WR-1065, lower affinity than for spermidine, about 10% of the rate with spermidine
-
-
?
acetyl-CoA + 6,6-difluorospermidine
CoA + N1-acetyl-6,6-difluorospermidine
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16.6% of the rate with spermidine
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-
?
acetyl-CoA + 7,7-difluorospermidine
CoA + N1-acetyl-7,7-difluorospermidine
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19.7% of the rate with spermidine
-
-
?
acetyl-CoA + amantadine
CoA + N1-acetylamantadine
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reaction occurs in vivo and in vitro, but only in presence of increased enzyme levels, amantadine may be a specific drug substrate for SSAT
-
?
acetyl-CoA + D-glucosamine 6-phosphate
CoA + N-acetyl-D-glucosamine 6-phosphate
-
-
-
?
acetyl-CoA + diethylenetriamine
CoA + N1-acetyl-diethylenetriamine
-
-
-
?
acetyl-CoA + eIF5A
CoA + acytyl-eIF5A
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-
selective acetylation of the hypusine and/or deoxyhypusine residue of translation initiation factor eIF5A, resulting in loss of eIF5A activity. Hypusine or deoxyhypusine, as the free amino acid, do not act as a substrate for isoform SSAT1
-
?
acetyl-CoA + N-(n-butyl)-1,3-diaminopropane
CoA + N1-acetyl-N3-(n-butyl)-1,3-diaminopropane
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weak substrate, lower affinity than for spermidine, 1.3% of the rate with spermidine
-
-
?
acetyl-CoA + N1-acetylspermidine
CoA + N1,N8-diacetylspermidine
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low affinity
-
-
?
acetyl-CoA + N1-dansylnorspermine
CoA + N1-acetyl-N1-dansylnorspermine
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the acetylation reaction proceeds by Bi-Bi mechanism
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-
?
acetyl-CoA + putrescine
CoA + acetylputrescine
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breakdown of spermidine and putrescine
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?
chloroacetyl-CoA + spermine
N1-spermine-acetyl-CoA + ?
N1-chloroacetylation of spermine performed by hSSAT protein, pH 7.5 and 2 microM recombinant human SSAT protein at room temperature for one hour, identity of the product confirmed by mass spectrometry
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-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
Q6GQM2
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-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
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?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
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-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
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-
-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
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-
-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
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-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
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-
-
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?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
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-
-
?
3 acetyl-CoA + spermidine
3 CoA + N1,N4,N8-triacetylspermidine
spermidine is preferred over spermine
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-
?
3 acetyl-CoA + spermidine
3 CoA + N1,N4,N8-triacetylspermidine
cased on structural and docking analysis, it is expected that Glu53 and Tyr93 are key residues for recognizing spermidine
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-
?
3 acetyl-CoA + spermidine
3 CoA + N1,N4,N8-triacetylspermidine
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-
-
?
3 acetyl-CoA + spermidine
3 CoA + N1,N4,N8-triacetylspermidine
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-
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?
acetyl-CoA + 1,12-diamino-3,6,9-triazadodecane
?
-
an extremely poor substrate of human recombinant SSAT2, that is metabolized by SSAT1 in Hep-G2 cells and in wild-type primary hepatocytes
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?
acetyl-CoA + 1,12-diamino-3,6,9-triazadodecane
?
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SSAT1 is the main acetylator of 1,12-diamino-3,6,9-triazadodecane compared to SSAT2
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?
acetyl-CoA + 1,12-diamino-3,6,9-triazadodecane
?
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SSAT1 is the main acetylator of 1,12-diamino-3,6,9-triazadodecane compared to SSAT2
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?
acetyl-CoA + 1,3-diaminopropane
CoA + N1-acetyl-1,3-diaminopropane
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ir
acetyl-CoA + 1,3-diaminopropane
CoA + N1-acetyl-1,3-diaminopropane
-
-
-
-
?
acetyl-CoA + 1,3-diaminopropane
CoA + N1-acetyl-1,3-diaminopropane
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-
-
?
acetyl-CoA + 1,3-diaminopropane
CoA + N1-acetyl-1,3-diaminopropane
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at a low rate
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-
?
acetyl-CoA + 1,5-diaminopentane
CoA + N1-acetyl-1,5-diaminopentane
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at 39% of the rate with putrescine
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-
?
acetyl-CoA + 1,5-diaminopentane
CoA + N1-acetyl-1,5-diaminopentane
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cadaverine
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ir
acetyl-CoA + 1,5-diaminopentane
CoA + N1-acetyl-1,5-diaminopentane
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-
-
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?
acetyl-CoA + 1,5-diaminopentane
CoA + N1-acetyl-1,5-diaminopentane
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at 45% of the rate with putrescine
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?
acetyl-CoA + 1,5-diaminopentane
CoA + N1-acetyl-1,5-diaminopentane
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-
-
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acetyl-CoA + 1,6-diaminohexane
CoA + N1-acetyl-1,6-diaminohexane
-
-
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ir
acetyl-CoA + 1,6-diaminohexane
CoA + N1-acetyl-1,6-diaminohexane
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at 50% of the rate with putrescine
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-
?
acetyl-CoA + 1,6-diaminohexane
CoA + N1-acetyl-1,6-diaminohexane
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at 74% of the rate with putrescine
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-
?
acetyl-CoA + histamine
CoA + N-acetylhistamine
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at about 30% of the rate with putrescine
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-
?
acetyl-CoA + histamine
CoA + N-acetylhistamine
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at about 30% of the rate with putrescine
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-
?
acetyl-CoA + N-acetylputrescine
CoA + N1,N4-diacetylputrescine
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-
-
-
?
acetyl-CoA + N1-acetylspermine
CoA + N1,N12-diacetylspermine
-
-
-
?
acetyl-CoA + N1-acetylspermine
CoA + N1,N12-diacetylspermine
-
-
-
-
?
acetyl-CoA + N1-acetylspermine
CoA + N1,N12-diacetylspermine
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reaction in vitro, but not in vivo
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ir
acetyl-CoA + putrescine
CoA + N-acetylputrescine
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preference for putrescine
-
?
acetyl-CoA + putrescine
CoA + N-acetylputrescine
-
-
-
?
acetyl-CoA + putrescine
CoA + N-acetylputrescine
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preference for putrescine
-
?
acetyl-CoA + putrescine
CoA + N-acetylputrescine
Trichosporon melibiosaceum CBS 6087
-
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetyl-spermidine
Q6GQM2
spermidine is preferred over spermine
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
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very poor substrate, at 2-4% of the rate with putrescine
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?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
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+ N8-acetylspermidine, ratio N1 acetylspermidine:N8-acetylspermidine is 50:45
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
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breakdown of spermidine and putrescine, key agent in the supply of nitrogen to the cell
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
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+ N8-acetylspermidine, ratio N1 acetylspermidine:N8-acetylspermidine is 50:45
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
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breakdown of spermidine and putrescine, key agent in the supply of nitrogen to the cell
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
-
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
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product is exclusively N1-acetylspermidine
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
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product is exclusively N1-acetylspermidine
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
-
product is exclusively N1-acetylspermidine
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
-
N1-acetylspermidine is the major product
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
spermidine acetylation might be a strategy for inhibiting growth in response to environmental stresses
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
catabolism of spermidine and spermine
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
catabolism of spermidine and spermine
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
mimics of transition state of SSAT1 reaction analyzed
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
-
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
-
product is exclusively N1-acetylspermidine
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
very poor substrate, at 2-4% of the rate with putrescine
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
-
product is exclusively N1-acetylspermidine
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
physiological substrate, higher rate than with spermine
product is exclusively N1-acetylspermidine
ir
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
spermidine and spermine may be physiological substrates, enzyme may play an important role in interconversion of polyamines
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
Trichosporon melibiosaceum CBS 6087
-
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
-
very poor substrate, at 2-4% of the rate with putrescine
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
Q6GQM2
spermidine is preferred over spermine
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
-
about 40% of the rate with spermidine
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
-
catabolism of spermidine and spermine
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
N1-acetylation of spermidine and spermine by spermidine/spermine acetyltransferase (SSAT) crucial for regulation of the cellular polyamine levels in eukaryotic cells
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
mimics of transition state of SSAT1 reaction analyzed
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
N1-acetylation of spermidine and spermine by spermidine/spermine acetyltransferase (SSAT) crucial for regulation of the cellular polyamine levels in eukaryotic cells, chemical and kinetic mechanism for acetyl transfer activity by recombinant human SSAT protein proposed
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
pharmacologic and genetic manipulation of keratin 6 (K6)-spermidine/spermine N1-acetyltransferase (SSAT) transgenic mice subjected to carcinogenesis
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
spermine and the enzyme and form a proton wire between the side chain of Glu92 and the N1 amine of spermine, a single water molecule forms hydrogen bonds with the side chains of Glu92, Asp93, and the N4 amine of spermine, substrate binding structure, overview
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
-
very poor substrate, at 2-4% of the rate with putrescine
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
-
physiological substrate, lower rate than with spermidine
-
ir
acetyl-CoA + spermine
CoA + N1-acetylspermine
-
spermidine and spermine may be physiological substrates, enzyme may play an important role in interconversion of polyamines
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
spermidine is preferred over spermine
-
-
?
acetyl-CoA + sym-norspermidine
CoA + N1-acetyl-sym-norspermidine
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identical with caldine
-
-
?
acetyl-CoA + sym-norspermidine
CoA + N1-acetyl-sym-norspermidine
-
-
-
-
?
acetyl-CoA + sym-norspermidine
CoA + N1-acetyl-sym-norspermidine
-
high affinity for sym-norspermidine
-
-
?
acetyl-CoA + sym-norspermine
CoA + N1-acetyl-sym-norspermine
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at a much lower rate than with sym-norspermidine
-
-
ir
acetyl-CoA + triethylenetetramine
?
-
SSAT2 is the main acetylator of TETA compared to SSAT1
-
-
?
acetyl-CoA + triethylenetetramine
?
-
SSAT2 is the main acetylator of TETA compared to SSAT1
-
-
?
additional information
?
-
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enzyme is involved in polyamine degradation and excretion of excessive polyamines, release of N-acetylputrescine, role in the control of polyamine concentrations
-
-
-
additional information
?
-
-
important function in the degradation of diamines of lower eukaryotes
-
-
-
additional information
?
-
-
not: methylamine, dimethylamine, di-n-butylamine, L-lysine, benzylamine, semicarbazide, L-serine, glyoxylate, oxaloacetate, 4-aminobenzoate, 2-aminobenzoate
-
-
-
additional information
?
-
-
not: methylamine, dimethylamine, di-n-butylamine, L-lysine, benzylamine, semicarbazide, L-serine, glyoxylate, oxaloacetate, 4-aminobenzoate, 2-aminobenzoate
-
-
-
additional information
?
-
-
polyamine-dependent protein synthesis is only found in isozymes Ssat1b and Ssat1c, not in Ssat1a. Also only Ssat1b and Ssat1c, but not the polyamine-insensitive Ssat1a, are able to interact with integrin alpha9 and Hif-1alpha. Substrate preferences of the isoenzymes are different. Ssat1b has similar Km values for spermidine and spermine, while Ssat1a has a smaller Km toward spermidine and Ssat1c has a smaller Km for spermine. Ssat1a and Ssatb have a better kcat/Km value for spermidine than that for spermine
-
-
-
additional information
?
-
Q6GQM2
polyamine-dependent protein synthesis is only found in isozymes Ssat1b and Ssat1c, not in Ssat1a. Also only Ssat1b and Ssat1c, but not the polyamine-insensitive Ssat1a, are able to interact with integrin alpha9 and Hif-1alpha. Substrate preferences of the isoenzymes are different. Ssat1b has similar Km values for spermidine and spermine, while Ssat1a has a smaller Km toward spermidine and Ssat1c has a smaller Km for spermine. Ssat1a and Ssatb have a better kcat/Km value for spermidine than that for spermine
-
-
-
additional information
?
-
spermine binding structure by X-ray diffraction scattering analysis, overview
-
-
-
additional information
?
-
-
Lys-141 is the first residue in a KRR motif that makes up part of the active site
-
-
-
additional information
?
-
-
enzyme requires a substrate with the structure H2N(CH2)3NHR and acetylates the primary amino group
-
-
-
additional information
?
-
-
acetylation is a physiological response to convert excess polyamines to a physiologically inert form which is readily excreted
-
-
-
additional information
?
-
-
enzyme plays an efficient role in maintaining polyamine pool homeostasis during challenges with exogenous polyamines
-
-
-
additional information
?
-
-
rate-limiting enzyme in the degradation and interconversion of polyamines
-
-
-
additional information
?
-
-
SSAT prevents overaccumulation of higher polyamines from becoming toxic to cell and maintains a balanced ratio of polyamines according to cellular needs
-
-
-
additional information
?
-
isozyme SSAT-2 shows very low activity in intact wild-type cells, but is equally active to isozyme SSAT-1 in recombinantly transfected cells
-
-
-
additional information
?
-
isozyme SSAT-2 shows very low activity in intact wild-type cells, but is equally active to isozyme SSAT-1 in recombinantly transfected cells
-
-
-
additional information
?
-
substrate specificity of isozyme SSAT-1 in descending order: norspermidine equal spermidine, spermine, N1-acetylspermine, putrescine
-
-
-
additional information
?
-
substrate specificity of isozyme SSAT-1 in descending order: norspermidine equal spermidine, spermine, N1-acetylspermine, putrescine
-
-
-
additional information
?
-
substrate specificity of isozyme SSAT-2 in descending order: norspermidine, spermidine equal spermine, N1-acetylspermine equal putrescine
-
-
-
additional information
?
-
substrate specificity of isozyme SSAT-2 in descending order: norspermidine, spermidine equal spermine, N1-acetylspermine equal putrescine
-
-
-
additional information
?
-
-
the enzyme functions as a coactivator for NF-kappaB and cooperates with CREB-binding protein and the p300/CBP-associated factor to enhance NF-kappaB-dependent transcription
-
-
-
additional information
?
-
-
polyamines regulate SSAT mRNA translational efficiency by inhibiting a repressor protein from binding to regions of the coding sequence of the SSAT transcript
-
-
-
additional information
?
-
roles of SSAT proteins in oxygen homeostasis, SSAT1 binding to hypoxia-inducible factor-1 (HIF-1alpha) promotes its ubiquitination/degradation, in contrast to SSAT2, SSAT1 acts by stabilizing the interaction of HIF-1alpha with RACK1
-
-
-
additional information
?
-
-
N1,N11-diethylnorspermine induces apoptosis involving increased SSAT activity and the mitochondria of the cell
-
-
-
additional information
?
-
-
simultaneous drug combination or quinoxaline pre-treatment synergistically increases SSAT expression, depletes polyamines, increases reactive oxygen species production, and produces synergistic tumor cell killing in both cell lines, overview. Cisplatin-resistant human ovarian cell line, A2780/CP cells, cannot be induced by spermidine analogues, in contrast to the sensitive counterpart A2780
-
-
-
additional information
?
-
-
SSAT binds to the HIF-1alpha subunit and promotes its ubiquitination and degradation. SSAT transcriptional regulation, regulation of SSAT protein levels by polyamines or analogues, SSAT protein turnover, overview. Upregulation of the Sat1 gene transcription is critical for the cell-specific polyamine or analog-mediated increase in SSAT content
-
-
-
additional information
?
-
-
SSAT expression causes arrest of cell cycle and cell growth in the S-phase in transfected cells through a mechanism involving the suppression of cyclin A and E2F1-expression, overview
-
-
-
additional information
?
-
-
SSAT induction increased metabolic flux by about 5fold, overview. The metabolic flux can be interrupted by inhibition of polyamine biosynthesis but not by inhibition of polyamine oxidation
-
-
-
additional information
?
-
-
the enzyme transforms polyamines into putrescine
-
-
-
additional information
?
-
human SSAT1 binds to the PAS-B (Per-ARNT-Sim) domain of HIF-1alpha, a key regulator of oxygen homeostasis in all metazoans, facilitating its degradation
-
-
-
additional information
?
-
-
SSAT catalyzes together with polyamine oxidase the back-conversion of spermine to spermidine and the latter to putrescine, a function lowering polyamine pools by facilitating their catabolism and excretion
-
-
-
additional information
?
-
-
enzyme plays an efficient role in maintaining polyamine pool homeostasis during challenges with exogenous polyamines
-
-
-
additional information
?
-
-
the enzyme is involved in intestinal tumorigenesis in ApcMin/+ MIN mice, enzyme is involved in catabolism of polyamines, activation of the enzyme in vivo results in suppression of tumor outgrowth in a mouse prostate cancer model
-
-
-
additional information
?
-
-
the enzyme is rate-limiting in polyamine catabolism
-
-
-
additional information
?
-
-
participates in polyamine homeostasis by regulating polyamine export and catabolism. Expression status of spermidine/spermine N1-acetyltransferase alters body fat accumulation by metabolically modulating tissue acetyl- and malonyl-CoA levels, thereby influencing fatty acid biosynthesis and oxidation
-
-
-
additional information
?
-
-
SSAT gene expression is fine-tuned by regulated unproductive splicing and translation, which is modulated by polyamine levels
-
-
-
additional information
?
-
-
regulation of SSAT protein levels by polyamines or analogues, overview
-
-
-
additional information
?
-
SSAT catalyzes the transfer of acetyl groups from acetylcoenzyme A to spermidine and spermine, as part of a polyamine degradation pathway. No activity with putrescine, cadaverine, lysine, thialysine, amantadine, substrate specificity, overview
-
-
-
additional information
?
-
-
enzyme is involved in polyamine degradation and excretion of excessive polyamines, release of N-acetylputrescine, role in the control of polyamine concentrations
-
-
-
additional information
?
-
-
enzyme requires a substrate with the structure H2N(CH2)3NHR and acetylates the primary amino group
-
-
-
additional information
?
-
-
regulation of SSAT protein levels by polyamines or analogues, overview
-
-
-
additional information
?
-
no substrates: glycine, glutamate, aspartate, leucine, alanine or arginine
-
-
-
additional information
?
-
spermine and spermidine are the preferential substrates, no activity with cadaverine. Conformational differences between enzyme SpeG ligand-free and liganded structures, allosteric substrate binding site structure, overview
-
-
-
additional information
?
-
-
spermine and spermidine are the preferential substrates, no activity with cadaverine. Conformational differences between enzyme SpeG ligand-free and liganded structures, allosteric substrate binding site structure, overview
-
-
-
additional information
?
-
substrate-induced allosteric change of quaternary structure of spermidine N-acetyltransferase SpeG, overview
-
-
-
additional information
?
-
-
substrate-induced allosteric change of quaternary structure of spermidine N-acetyltransferase SpeG, overview
-
-
-
additional information
?
-
substrate-induced allosteric change of quaternary structure of spermidine N-acetyltransferase SpeG, overview
-
-
-
additional information
?
-
spermine and spermidine are the preferential substrates, no activity with cadaverine. Conformational differences between enzyme SpeG ligand-free and liganded structures, allosteric substrate binding site structure, overview
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
acetyl-CoA + amantadine
CoA + N1-acetylamantadine
-
reaction occurs in vivo and in vitro, but only in presence of increased enzyme levels, amantadine may be a specific drug substrate for SSAT
-
?
acetyl-CoA + eIF5A
CoA + acytyl-eIF5A
-
-
selective acetylation of the hypusine and/or deoxyhypusine residue of translation initiation factor eIF5A, resulting in loss of eIF5A activity. Hypusine or deoxyhypusine, as the free amino acid, do not act as a substrate for isoform SSAT1
-
?
acetyl-CoA + putrescine
CoA + acetylputrescine
-
breakdown of spermidine and putrescine
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
Q6GQM2
-
-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
-
-
-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
P21673
-
-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
-
-
-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
-
-
-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
Q9KL03
-
-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
-
-
-
-
?
3 acetyl-CoA + 2 spermine
3 CoA + N1-acetylspermine + N1,N12-diacetylspermine
Q9KL03
-
-
-
?
3 acetyl-CoA + spermidine
3 CoA + N1,N4,N8-triacetylspermidine
Q9KL03
-
-
-
?
3 acetyl-CoA + spermidine
3 CoA + N1,N4,N8-triacetylspermidine
Q9KL03
-
-
-
?
acetyl-CoA + 1,12-diamino-3,6,9-triazadodecane
?
-
an extremely poor substrate of human recombinant SSAT2, that is metabolized by SSAT1 in Hep-G2 cells and in wild-type primary hepatocytes
-
-
?
acetyl-CoA + 1,12-diamino-3,6,9-triazadodecane
?
-
SSAT1 is the main acetylator of 1,12-diamino-3,6,9-triazadodecane compared to SSAT2
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
breakdown of spermidine and putrescine, key agent in the supply of nitrogen to the cell
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
breakdown of spermidine and putrescine, key agent in the supply of nitrogen to the cell
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
spermidine acetylation might be a strategy for inhibiting growth in response to environmental stresses
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
catabolism of spermidine and spermine
-
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
catabolism of spermidine and spermine
-
?
acetyl-CoA + spermidine
CoA + N1-acetylspermidine
-
spermidine and spermine may be physiological substrates, enzyme may play an important role in interconversion of polyamines
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
-
catabolism of spermidine and spermine
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
P21673
N1-acetylation of spermidine and spermine by spermidine/spermine acetyltransferase (SSAT) crucial for regulation of the cellular polyamine levels in eukaryotic cells
-
-
?
acetyl-CoA + spermine
CoA + N1-acetylspermine
-
spermidine and spermine may be physiological substrates, enzyme may play an important role in interconversion of polyamines
-
-
?
acetyl-CoA + triethylenetetramine
?
-
SSAT2 is the main acetylator of TETA compared to SSAT1
-
-
?
acetyl-CoA + triethylenetetramine
?
-
SSAT2 is the main acetylator of TETA compared to SSAT1
-
-
?
additional information
?
-
-
enzyme is involved in polyamine degradation and excretion of excessive polyamines, release of N-acetylputrescine, role in the control of polyamine concentrations
-
-
-
additional information
?
-
-
important function in the degradation of diamines of lower eukaryotes
-
-
-
additional information
?
-
-
acetylation is a physiological response to convert excess polyamines to a physiologically inert form which is readily excreted
-
-
-
additional information
?
-
-
enzyme plays an efficient role in maintaining polyamine pool homeostasis during challenges with exogenous polyamines
-
-
-
additional information
?
-
-
rate-limiting enzyme in the degradation and interconversion of polyamines
-
-
-
additional information
?
-
-
SSAT prevents overaccumulation of higher polyamines from becoming toxic to cell and maintains a balanced ratio of polyamines according to cellular needs
-
-
-
additional information
?
-
P21673
isozyme SSAT-2 shows very low activity in intact wild-type cells, but is equally active to isozyme SSAT-1 in recombinantly transfected cells
-
-
-
additional information
?
-
Q96F10
isozyme SSAT-2 shows very low activity in intact wild-type cells, but is equally active to isozyme SSAT-1 in recombinantly transfected cells
-
-
-
additional information
?
-
-
the enzyme functions as a coactivator for NF-kappaB and cooperates with CREB-binding protein and the p300/CBP-associated factor to enhance NF-kappaB-dependent transcription
-
-
-
additional information
?
-
-
N1,N11-diethylnorspermine induces apoptosis involving increased SSAT activity and the mitochondria of the cell
-
-
-
additional information
?
-
-
simultaneous drug combination or quinoxaline pre-treatment synergistically increases SSAT expression, depletes polyamines, increases reactive oxygen species production, and produces synergistic tumor cell killing in both cell lines, overview. Cisplatin-resistant human ovarian cell line, A2780/CP cells, cannot be induced by spermidine analogues, in contrast to the sensitive counterpart A2780
-
-
-
additional information
?
-
-
SSAT binds to the HIF-1alpha subunit and promotes its ubiquitination and degradation. SSAT transcriptional regulation, regulation of SSAT protein levels by polyamines or analogues, SSAT protein turnover, overview. Upregulation of the Sat1 gene transcription is critical for the cell-specific polyamine or analog-mediated increase in SSAT content
-
-
-
additional information
?
-
-
SSAT expression causes arrest of cell cycle and cell growth in the S-phase in transfected cells through a mechanism involving the suppression of cyclin A and E2F1-expression, overview
-
-
-
additional information
?
-
-
SSAT induction increased metabolic flux by about 5fold, overview. The metabolic flux can be interrupted by inhibition of polyamine biosynthesis but not by inhibition of polyamine oxidation
-
-
-
additional information
?
-
-
the enzyme transforms polyamines into putrescine
-
-
-
additional information
?
-
-
SSAT catalyzes together with polyamine oxidase the back-conversion of spermine to spermidine and the latter to putrescine, a function lowering polyamine pools by facilitating their catabolism and excretion
-
-
-
additional information
?
-
-
enzyme plays an efficient role in maintaining polyamine pool homeostasis during challenges with exogenous polyamines
-
-
-
additional information
?
-
-
the enzyme is involved in intestinal tumorigenesis in ApcMin/+ MIN mice, enzyme is involved in catabolism of polyamines, activation of the enzyme in vivo results in suppression of tumor outgrowth in a mouse prostate cancer model
-
-
-
additional information
?
-
-
the enzyme is rate-limiting in polyamine catabolism
-
-
-
additional information
?
-
-
participates in polyamine homeostasis by regulating polyamine export and catabolism. Expression status of spermidine/spermine N1-acetyltransferase alters body fat accumulation by metabolically modulating tissue acetyl- and malonyl-CoA levels, thereby influencing fatty acid biosynthesis and oxidation
-
-
-
additional information
?
-
-
SSAT gene expression is fine-tuned by regulated unproductive splicing and translation, which is modulated by polyamine levels
-
-
-
additional information
?
-
-
regulation of SSAT protein levels by polyamines or analogues, overview
-
-
-
additional information
?
-
P48026
SSAT catalyzes the transfer of acetyl groups from acetylcoenzyme A to spermidine and spermine, as part of a polyamine degradation pathway. No activity with putrescine, cadaverine, lysine, thialysine, amantadine, substrate specificity, overview
-
-
-
additional information
?
-
-
enzyme is involved in polyamine degradation and excretion of excessive polyamines, release of N-acetylputrescine, role in the control of polyamine concentrations
-
-
-
additional information
?
-
-
regulation of SSAT protein levels by polyamines or analogues, overview
-
-
-
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
acetyl-CoA
cofactor-binding site structure, overview. The beta-bulge formed by the beta4 and beta5 parallel strands is where the pantotheine moiety of AcCoA is located in the active site, characteristic for members of the GNAT superfamily. The pantothenate moiety forms hydrogen bonds with two conserved residues Ile87 and Ile89
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
amantadine
-
competitively inhibits spermidine acetylation, at 10 mM: complete inhibition
N1-spermine-acetyl-CoA
bisubstrate analogue, bisubstrate inhibition patterns determined, linear, competitive inhibition against sperimidine and acetyl-CoA determined
Berenil
-
competitive with respect to putrescine, i.e. diminazene aceturate
additional information
-
folate cycle inhibitors, with quinoxaline moieties 3-methyl-7-trifluoromethyl-2(R)-[3,4,5-trimethoxyanilino]-quinoxaline or 3-piperazinilmethyl-2[4(oxymethyl)-phenoxy]quinoxaline, affect the enzyme, simultaneous drug combination or quinoxaline pre-treatment synergistically increases SSAT expression, depletes polyamines, increases reactive oxygen species production, and produces synergistic tumor cell killing in both cell lines, overview
-
additional information
-
synthetic peptide IVEMSTSKTGK50HGHAK modeled on the sequence of amino acids surrounding the hypusine residue K50, 50% inhibition of eIF5A acetylation at 0.05 mM
-
additional information
-
conjugates of symmetrical polyamines spermine , 1,12-diamino-4,9-diazadodecane and of nor-spermidine, 1,7-diamino-4-azaheptane, with coenzyme A, mimicking intermediate the coenzyme-substrate complex, are synthesized to inhibit the enzyme, overview
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
N1,N11-bis(ethyl)-norspermidine
increases SSAT activity, tumor regression analyzed in tumor-bearing transgenic mice expressing SSAT, tumor regression not enhanced by treatment with
N1,N11-bis(ethyl)norspermine
-
polyamine analogue, about 300fold activation of wild-type enzyme, 4fold activation of mutant L156F, the compound highly stabilizes the wild-type enzyme preventing it from degradation, while the effect on degradation of the mutant enzyme is smaller
N1,N11-bis-(ethyl)-norspermine
-
induces mRNA and activity of SSAT protein, translation proceeded by competition of a predicted RNA-binding protein
N1,N11-diethylnorspermine
-
polyamine analogue with clinical relevance as an experimental anticancer agent. Treatment of human C-28/I2 chondrocytes rapidly induces spermidine/spermine N1-acetyltransferase and spermine oxidase activities, and down-regulates ornithine decarboxylase. The treatment does not provoke cell death and caspase activation when given alone for 24 h, but causes a caspase-3 and -9 dependent apoptosis in chondrocytes further exposed to cycloheximide. The simultaneous addition of N1,N11-diethylnorspermine and cycloheximide rapidly increases caspase activity in C-28/I2 cells in the absence of spermidine/spermineN1-acetyltransferase and spermine oxidase induction or significant reduction of polyamine levels. Caspase activation induced by N1,N11-diethylnorspermine plus cycloheximide is not prevented by a N1-acetylpolyamine oxidase inhibitor
additional information
-
certain stresses induce enzyme by a spermidine-dependent post-transcriptional mechanism, e.g. heat shock, diethyldithiocarbamate and high levels of endogenous spermidine, alpha-difluoromethylornithine inhibits stress induction
-
additional information
-
enzyme is induced by methylglyoxal bis(guanylhydrazone), potentiated by tetronasin or felodipine, tetronasin is also an active inducer, induction is related to the concentration of intracellular free calcium
-
additional information
-
enzyme is induced by isopropyl beta-D-thiogalactopyranoside; N1,N12-bis(ethyl)spermine is a potent inducer of enzyme in human tumor cells
-
additional information
-
enzyme is induced by isopropyl beta-D-thiogalactopyranoside
-
additional information
-
certain stresses induce enzyme by a spermidine-dependent post-transcriptional mechanism, e.g. heat shock, diethyldithiocarbamate and high levels of endogenous spermidine, alpha-difluoromethylornithine inhibits stress induction
-
additional information
-
N1,N11-diethylnorspermine induces SSAT mRNA and activity
-
additional information
-
enzyme is highly inducible by polyamine analogues such as N1,N12-bis(ethyl)spermine and N1,N11-bis(ethyl)norspermine, they prevent enzyme degradation via the Ub/proteasome pathway, mechanism
-
additional information
-
indomethacin and excess polyamines induce SSAT activity
-
additional information
-
amino acid deprivation upregulates enzyme expression level of 2 different mRNA forms
-
additional information
-
N1,N11-diethylnorspermine induces SSAT mRNA and activity
-
additional information
-
N1,N11-diethylnorspermine induces SSAT activity by post-mRNA regulation
-
additional information
-
enzyme is induced by treatment with hepatotoxins, e.g. carbon tetrachloride
-
additional information
-
enzyme is induced by growth hormone, thioacetamide, dialkylnitrosamines, folic acid and spermidine; enzyme is induced by treatment with hepatotoxins, e.g. carbon tetrachloride
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.106
1,12-diamino-3,6,9-triazadodecane
-
pH and temperature not specified in the publication
0.194
diethylenetriamine
measured at fixed saturating concentrations of acetyl-CoA
0.196
ethylenediamine
measured at fixed saturating concentrations of acetyl-CoA
0.083
triethylenetetramine
-
pH and temperature not specified in the publication
0.107
1,3-Diaminopropane
measured at fixed saturating concentrations of acetyl-CoA
0.0038
acetyl-CoA
measured at fixed saturating concentration of spermidine
0.022
spermidine
measured at fixed saturating concentrations of acetyl-CoA
0.09
spermidine
Q6GQM2
isozyme ssat1b, pH and temperature not specified in the publication
0.182
spermidine
Q6GQM2
isozyme ssat1a, pH and temperature not specified in the publication
0.232
spermidine
Q6GQM2
isozyme ssat1c, pH and temperature not specified in the publication
0.0057
spermine
measured at fixed saturating concentrations of acetyl-CoA
0.055
spermine
Q6GQM2
isozyme ssat1a, pH and temperature not specified in the publication
0.091
spermine
Q6GQM2
isozyme ssat1b, pH and temperature not specified in the publication
0.139
spermine
Q6GQM2
isozyme ssat1c, pH and temperature not specified in the publication
additional information
additional information
no detectable activity for putrescine and cadaverine
-
additional information
additional information
-
Km value for spermine is lower than that for N1-acetylspermine
-
additional information
additional information
allosteric substrate binding, polyamine allosteric site structure, complex enzyme behavior, it exhibits sigmoidal curves and substrate inhibition, bireactant random steady-state kinetic mechanism, detailed non-linear regression kinetic analysis, overview
-
additional information
additional information
-
allosteric substrate binding, polyamine allosteric site structure, complex enzyme behavior, it exhibits sigmoidal curves and substrate inhibition, bireactant random steady-state kinetic mechanism, detailed non-linear regression kinetic analysis, overview
-
additional information
additional information
allosteric substrate binding, bireactant random steady-state kinetic mechanism
-
additional information
additional information
-
allosteric substrate binding, bireactant random steady-state kinetic mechanism
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.5
spermidine
Q6GQM2
isozyme ssat1c, pH and temperature not specified in the publication
34.1
spermidine
Q6GQM2
isozyme ssat1b, pH and temperature not specified in the publication
122.2
spermidine
Q6GQM2
isozyme ssat1a, pH and temperature not specified in the publication
1.9
spermine
Q6GQM2
isozyme ssat1c, pH and temperature not specified in the publication
4.3
spermine
Q6GQM2
isozyme ssat1b, pH and temperature not specified in the publication
62.4
spermine
Q6GQM2
isozyme ssat1a, pH and temperature not specified in the publication
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.006
N1-spermine-acetyl-CoA
bisubstrate analogue, linear, competitive inhibition, structure of hSSAT with bound N1-spermine-acetyl-CoA determined
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.000003 - 0.00008
-
activity in different clones of a transfected rat epidermal cell line expressing the enzyme
0.00007
recombinant HEK-293 cells expressing isozyme SSAT-2, substrate putrescine; recombinant HEK-293 cells expressing isozyme SSAT-2, substrate putrescine
0.00008
recombinant HEK-293 cells expressing isozyme SSAT-2, substrate N1-acetylspermine; recombinant HEK-293 cells expressing isozyme SSAT-2, substrate N1-acetylspermine
0.0002
recombinant HEK-293 cells expressing isozyme SSAT-1, substrate N1-acetylspermine
0.00023
recombinant HEK-293 cells expressing isozyme SSAT-2, substrate spermine; recombinant HEK-293 cells expressing isozyme SSAT-2, substrate spermine
0.00025
recombinant HEK-293 cells expressing isozyme SSAT-2, substrate spermidine; recombinant HEK-293 cells expressing isozyme SSAT-2, substrate spermidine
0.0004
recombinant HEK-293 cells expressing isozyme SSAT-1, substrate spermine
0.00068
recombinant HEK-293 cells expressing isozyme SSAT-2, substrate norspermidine; recombinant HEK-293 cells expressing isozyme SSAT-2, substrate norspermidine
0.001
recombinant HEK-293 cells expressing isozyme SSAT-1, substrate spermidine
0.0011
recombinant HEK-293 cells expressing isozyme SSAT-1, substrate norspermidine
0.0012
-
recombinant EGFP-tagged SSAT in cells in presence of N'-ethyl-N''-[(cyclopropyl)-methy]-4,8-diazaundecane
0.0058
-
recombinant EGFP-tagged SSAT in cells in presence of N'-ethyl-N''-[(cycloheptyl)methy]-4,8-diazaundecane
0.0106
-
recombinant EGFP-tagged SSAT in cells in presence of N',N''-diethylnorspermine
additional information
additional information
kinetic and mechanistic characterization, determination of bisubstrate inhibition patterns, three-dimensional structure of the recombinant human SSAT protein with bound bisubstrate inhibitor, acid/base assisted reaction catalyzed by SSAT involves a ternary complex, proposed on the base of kinetic properties, pH dependence and structure analysis
additional information
-
regulation of SSAT expression, de novo RNA and protein synthesis analyzed, two regions of the SSAT protein coding sequence involved in translational repression of SSAT in the absence of elevated polyamine levels, RNA-binding protein possibly interacting with stem-loop structures to block translation can be displaced by the polyamine analogue N1,N11-bis-(ethyl)-norspermine (DENSPM), allowing translation to proceed, 5' and 3' polyamine-responsive regions interact with each other in vivo, changes in either region result in translation in the absence of the polyamine analogue N1,N11-bis-(ethyl)-norspermine
additional information
SSAT1 inhibits hypoxia-inducible factor-1 (HIF-1alpha) through protein/protein interaction, effect of SSAT1 loss of function on HIF-1alpha protein levels and HIF-1 transcriptional activity, mutation of Arg101 impairs SSAT1-mediated HIF-1alpha degradation, SSAT1 promotes the ubiquitination of HIF-1alpha, involvement of SSAT1 and SSAT2 in alternative pathways for ubiquitination and degradation of HIF-1alpha, complementary roles in promoting O2-independent and O2-dependent degradation of HIF-1alpha
additional information
-
structure of polyamine fragment of the conjugate important for enzyme activity, existence of adenosine groups crucial for effective inhibition, since conjugates of D-N-pantothenylamidoethyl mercaptane family reveals low inhibitory activities, most exact mimic of the intermediate of N1-acetyltransferase reaction less active than analogue of the intermediate of N8-acetyltransferase reaction, significant contribution of the polyamine fragment into inhibition proven by lower activity
additional information
-
polyamine content in different clones of a transfected rat epidermal cell line expressing the enzyme, overview
additional information
tumor progression in transgenic mice expressing SSAT depends on elevated activity of ornithine decarboxylase (ODC) and on increased putrescine levels, strategy to modulate polyamine levels through the inhibition of ornithine decarboxylase (ODC) activity or polyamine uptake, but not via increased SSAT expression for cancer chemoprevention
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
7.8
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.7 - 9.1
activity monitored every 0.3 pH units, bell shaped pH activity profile, depending on ionization state of two groups with apparent pKa values of 7.27 and 8.87
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
30
37
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
Ssat1; three homologous ssat1 genes, named ssat1a, ssat1b, and ssat1c
Q6GQM2
UniProt
brenda
-
487262, 487265, 487268, 487270, 661893, 671226, 671847, 672359, 672937, 674623, 675916, 676840, 702524, 703035, 703097, 703928, 704455, 706022, 712558
-
-
brenda
2 isozymes SSAT-1 and SSAT-2; isozyme SSAT-1; 2 isozymes SSAT-1 and SSAT-2
UniProt
brenda
keratin 6 (K6)-spermidine/spermine N1-acetyltransferase (SSAT) transgenic mice, B6D2F2 background
SwissProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
in breast tumors, SSAT is increased contributing to an increase in acetylated polyamines
brenda
-
high ratio of splice variant SSATX to SSAT mRNA in syngenic rats
brenda
-
the enzyme is inducible in response to 5-fluorouracil or oxaliplatin in parental and drugresistant HCT116 cell lines
brenda
-
high ratio of splice variant SSATX to SSAT mRNA in syngenic rats
brenda
-
TNFalpha can lead to the induction of NFkappaB signaling with a concomitant increase in spermidine/spermine N1-acetyltransferase expression
brenda
-
A549 and H157. TNFalpha can lead to the induction of NFkappaB signaling with a concomitant increase in spermidine/spermine N1-acetyltransferase expression
brenda
additional information
-
TNFalpha can lead to the induction of NFkappaB signaling with a concomitant increase in spermidine/spermine N1-acetyltransferase expression
brenda
-
enzyme expression in reduced in brain Brodmann areas,i.e. in BA4, BA8/9, and BA11, of suicide completers
brenda
-
induction by aspirin and different non-steroidal anti-inflammatory drugs
brenda
-
synovial fibroblasts from patients with rheumatoid arthritis or osteoarthritis
brenda
-
activity of SSAT is increased 28fold in tetracycline-induced cells. Increase in SSAT levels in HEK-293 cells leads to depletion of polyamines and elevation in the enzymatic activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, suggestive of a compensatory reaction to increased polyamine catabolism. Increased expression of SSAT also leads to DNA damage and G2 arrest
brenda
-
high ratio of splice variant SSATX to SSAT mRNA in syngenic rats
brenda
-
expression status of spermidine/spermine N1-acetyltransferase alters body fat accumulation by metabolically modulating tissue acetyl- and malonyl-CoA levels, thereby influencing fatty acid biosynthesis and oxidation
brenda
-
low ratio of splice variant SSATX to SSAT mRNA in syngenic rats
brenda
additional information
-
genes ssat1a, ssat1b, and ssat1c ares ubiquitously expressed in fish tissues st different levels, expression patterns, overview
brenda
additional information
Q6GQM2
genes ssat1a, ssat1b, and ssat1c ares ubiquitously expressed in fish tissues st different levels, expression patterns, overview
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
recombinant enzyme, expressed in Escherichia coli DH5alpha, is present at a level of about 2% of the soluble protein
-
brenda
-
mitochondrial uptake may be regulated by the phosphorylation state of SSAT
brenda
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
the enzyme is a member of the Gcn5-related N-acetyltransferase superfamily
evolution
the enzyme is a member of the Gcn5-related N-acetyltransferase superfamily. The open and intermediate states of ligand-free enzyme have a unique open dodecameric ring. The SpeG dodecamer is asymmetric except for the one 2fold axis and is unlike any known dodecameric structure. The SpeG dodecamer is conserved in different bacterial species, structure analysis and comparisons, overview
evolution
Q6GQM2
phylogenetic analysis of ssat-like genes dividing the genes into 3 clusters, comparison of zebrafish and human gene sequences and regulation, overview. Zebrafish ssat1 homologues are paralogous genes which experience subfunctionalization in their function and regulation
evolution
phylogenetic analysis of ssat-like genes dividing the genes into 3 clusters, comparison of zebrafish and human gene sequences and regulation, overview
evolution
-
the enzyme is a member of the Gcn5-related N-acetyltransferase superfamily; the enzyme is a member of the Gcn5-related N-acetyltransferase superfamily. The open and intermediate states of ligand-free enzyme have a unique open dodecameric ring. The SpeG dodecamer is asymmetric except for the one 2fold axis and is unlike any known dodecameric structure. The SpeG dodecamer is conserved in different bacterial species, structure analysis and comparisons, overview
-
malfunction
-
altered expression of SAT1 in the polyamine stress response, across multiple brain regions between control individuals and depressed individuals who have died by suicide, overview
malfunction
-
SSAT overexpression may be linked to the rare X-linked disease keratosis follicularis spinulosa decalvans
malfunction
-
enzyme inhibition also inhibits ongoing joint destruction. Enzyme inhibition or gene silencing by transfection of siRNA targeting SSAT-1 increases 5-methylcytosine levels/PMF-1 promoter methylation within 21 days
malfunction
-
key polyamine catabolic enzyme spermidine/spermine N1-acetyltransferase1 overexpression in HEK293T cells via adenoviral vector leads to a rapid depletion of spermidine and spermine, arrest in cell growth and a decline in cell viability. AdSAT1-transduced cells reveal morphological changes commonly associated with apoptosis, including cell shrinkage, nuclear fragmentation, mitochondrial alteration, vacuolization and membrane blebbing. As polyamine analogues, alpha-methylspermidine and N1,N12-dimethylspermine that are not substrates for SAT1 partially restore growth and prevent apoptosis of AdSAT1-transduced cells. Inhibition of polyamine oxidases does not restore the growth of AdSAT1-transduced cells or block apoptosis. AdSAT1-transduction causes apoptosis by an intrinsic mitochondrial pathway, release of cytochrome c from mitochondria to cytoplasm concomitant with a decrease in the mitochondrial fraction in AdSAT1-transduced cells
malfunction
-
SSAT1 knockdown leads to a dramatic reduction of N1-acetyylspermidine and N1-acetylspermine pools. Metabolism of 1,12-diamino-3,6,9-triazadodecane to N1-acetyl-1,12-diamino-3,6,9-triazadodecane is reduced with SSAT1 but not with SSAT2 shRNA. No metabolism of 1,12-diamino-3,6,9-triazadodecane detectable in SSAT1-KO cells. In wild-type cells, SSAT2 knockdown does not reduce the metabolism of 1,12-diamino-3,6,9-triazadodecane to N1-AcSpmTrien. In fact it leads to the induction of SSAT1 activity and increased metabolism of 1,12-diamino-3,6,9-triazadodecane to N1-acetyl-1,12-diamino-3,6,9-triazadodecane
malfunction
-
acetylation of triethylenetetramine is increased in SSAT1-overexpressing mice compared with wild-type mice, but SSAT1-deficient mice metabolize TETA at the same rate as the wild-type mice, due to the activity of thialysine acetyltransferase (SSAT2)
malfunction
-
the enzyme is underexpressed in brains from suicide victims compared to controls
malfunction
-
body weights, femur and tibia lengths and diameters, and ash weights of tibia of wild-type, SSAT overexpressing, and SSAT deficient female mice, overview. Enzyme overexpressing SSAT mice have an altered skeletal appearance with increased collagen cleavage and reduced bone strength compared to the wild-type. Engineered mice also show altered differentiation of mesenchymal stromal cells to osteoblasts. Polyamine metabolism of SSAT osteoblasts is disturbed. Osteoblasts of SSAT overexpressing mice show significantly increased SSAT enzyme activity
malfunction
-
body weights, femur and tibia lengths and diameters, and ash weights of tibia of wild-type, SSAT overexpressing, and SSAT deficient female mice, overview. Enzyme overexpressing SSAT mice have an altered skeletal appearance with increased collagen cleavage and reduced bone strength compared to the wild-type. Engineered mice also show altered differentiation of mesenchymal stromal cells to osteoblasts. Polyamine metabolism of SSAT osteoblasts is disturbed. Osteoblasts of SSAT overexpressing mice show significantly increased SSAT enzyme activity
-
metabolism
-
SSAT is the key enzyme in the catabolism of polyamines, and is turned over rapidly with only a low amount of enzyme present in the cell. Analogue-affected regulation of SSAT expression occurrs, mainly, after transcription. Depleted intracellular spermidine and spermine levels inversely correlate with the SSAT activity
metabolism
-
SSAT catalyzes the transfer of acetyl groups from acetylcoenzyme A to spermidine and spermine, as part of a polyamine degradation pathway
metabolism
-
acetylation of triethylenetetramine is increased in SSAT1-overexpressing mice compared with wild-type mice, but SSAT1-deficient mice metabolize TETA at the same rate as the wild-type mice, due to the activity of thialysine acetyltransferase (SSAT2)
metabolism
the enzyme is involved in regulation of polyamine levels in bacteria during pathogenesis
metabolism
Q6GQM2
spermidine/spermine N1-acetyltransferase 1 is a key enzyme in the polyamine interconversion pathway, which maintains polyamine homeostasis
metabolism
spermidine/spermine N1-acetyltransferase 1 is a key enzyme in the polyamine interconversion pathway, which maintains polyamine homeostasis
metabolism
-
the enzyme is involved in regulation of polyamine levels in bacteria during pathogenesis
-
physiological function
-
SAT1 is the rate-limiting enzyme involved in catabolism of the polyamines spermidine and spermine
physiological function
-
SSAT regulates cellular polyamine content and links polyamine metabolism to lipid and carbohydrate metabolism by means of alterations in the content of acetyl-CoA and ATP. Since polyamines play critical roles in normal and neoplastic growth and in ion channel regulation, SSAT is a key enzyme in these processes. A high level of SSAT stimulates flux through the polyamine biosynthetic pathway
physiological function
-
SSAT regulates cellular polyamine content and links polyamine metabolism to lipid and carbohydrate metabolism by means of alterations in the content of acetyl-CoA and ATP. Since polyamines play critical roles in normal and neoplastic growth and in ion channel regulation, SSAT is a key enzyme in these processes. A high level of SSAT stimulates flux through the polyamine biosynthetic pathway
physiological function
-
SSAT regulates cellular polyamine content and links polyamine metabolism to lipid and carbohydrate metabolism by means of alterations in the content of acetyl-CoA and ATP. Since polyamines play critical roles in normal and neoplastic growth and in ion channel regulation, SSAT is a key enzyme in these processes. A high level of SSAT stimulates flux through the polyamine biosynthetic pathway
physiological function
-
compared with wild-typet mice, the enzyme-deficient mice subjected to endotoxic acute kidney injury have less severe kidney damage as indicated by better preservation of kidney function. Animals treated with MDL72527, an inhibitor of both polyamine oxidase and spermine oxidase, show significant protection against endotoxin-induced acute kidney injury. Increased polyamine catabolism may contribute to kidney damage through generation of by-products of polyamine oxidation
physiological function
-
silencing the expression of alternative mRNA splice variant SSATX with small interfering RNA leads to increased enzymic activity. Transfection of enzyme-deficient cells with mutated SSAT gene which produces only trace amounts of alternative mRNA splice variant SSATX yields higher enzyme activity than transfection with the natural gene which produces both SSAT and SSATX. Blocking nonsense-mediated mRNA decay in vivo by protein synthesis inhibitor cycloheximide results in accumulation of SSATX mRNA, and like in cell culture, the increase of SSATX mRNA is prevented by administration of polyamine analog N1,N11-diethylnorspermine. Although SSATX/total SSAT mRNA ratio does not correlate with polyamine levels or SSAT activity between different tissues, increasing polyamine levels by methylspermidine or zink sulfate in a given tissue leads to decreased SSATX/total SSAT mRNA ratio and vice versa
physiological function
-
a key enzyme that transfers the acetyl group from acetyl-CoA to either the N-1 or N-8 position of spermidine, thereby reducing the intracellular polyamine level
physiological function
-
polyamines (agmatine, putrescine, spermine and spermidine) are ubiquitous molecules involved in cell growth and differentiation. They modulate neurotransmission and are responsible for the polyamine mediated stress response, a cascade of molecular events transiently activated by acute stress stimuli. Chronic stress can lead to a hyperactivation of the polyamine system, ultimately leading to cell growth inhibition and cell death. Spermidine/spermine N1-acetyltranserare 1 is the key regulator of cellular polyamine content and is involved in the catabolism of spermidine and spermine, a key step in the maintenance of polyamine homeostasis
physiological function
the enzyme catalyzes the initial step in the degradation of polyamines and is a critical enzyme for determining the polyamine concentrations in bacteria
physiological function
enzyme SpeG has an allosteric polyamine-binding site and acetylating polyamines regulate their intracellular concentrations
physiological function
Q6GQM2
Ssat1b and Ssat1c might not only be a polyamine metabolic enzyme but also simultaneously respond to polyamine levels and engage in cross-talk with other signaling pathways. They interact with a mammalian specific integrin alpha9 and Hif-1alpha, a key regulator of oxygen homeostasis in all metazoans
physiological function
the enzyme maintains polyamine homeostasis, mammalian Ssat1 is also involved in many physiological and pathological events such as hypoxia, cell migration, and carcinogenesis
physiological function
-
spermidine/spermine N1-acetyltransferase is a catabolic regulator of polyamines, ubiquitous molecules essential for cell proliferation and differentiation. Role of polyamine metabolism in bone remodeling
physiological function
the enzyme is involved in the negative control of sporulation and degradative enzyme production
physiological function
-
spermidine/spermine N1-acetyltransferase is a catabolic regulator of polyamines, ubiquitous molecules essential for cell proliferation and differentiation. Role of polyamine metabolism in bone remodeling
-
physiological function
-
enzyme SpeG has an allosteric polyamine-binding site and acetylating polyamines regulate their intracellular concentrations; the enzyme catalyzes the initial step in the degradation of polyamines and is a critical enzyme for determining the polyamine concentrations in bacteria
-
additional information
enzyme SpeG forms dodecamers in solution and in crystals, three-dimensional structure in several ligand-free and liganded structures, the enzyme occurs in open and closed conformations, overview. Conserved residue Tyr134 is proposed to function as the general acid to protonate the thiolate anion of CoA after transfer of the acetyl group to the substrate
additional information
-
enzyme SpeG forms dodecamers in solution and in crystals, three-dimensional structure in several ligand-free and liganded structures, the enzyme occurs in open and closed conformations, overview. Conserved residue Tyr134 is proposed to function as the general acid to protonate the thiolate anion of CoA after transfer of the acetyl group to the substrate
additional information
-
enzyme SpeG forms dodecamers in solution and in crystals, three-dimensional structure in several ligand-free and liganded structures, the enzyme occurs in open and closed conformations, overview. Conserved residue Tyr134 is proposed to function as the general acid to protonate the thiolate anion of CoA after transfer of the acetyl group to the substrate
-
Show AA Sequence and Transmembrane Helices (1978 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
Escherichia coli (strain K12)
Thermoplasma acidophilum (strain ATCC 25905 / DSM 1728 / JCM 9062 / NBRC 15155 / AMRC-C165)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Thermoplasma acidophilum (strain ATCC 25905 / DSM 1728 / JCM 9062 / NBRC 15155 / AMRC-C165)
Thermoplasma acidophilum (strain ATCC 25905 / DSM 1728 / JCM 9062 / NBRC 15155 / AMRC-C165)
Thermoplasma acidophilum (strain ATCC 25905 / DSM 1728 / JCM 9062 / NBRC 15155 / AMRC-C165)
Thermoplasma acidophilum (strain ATCC 25905 / DSM 1728 / JCM 9062 / NBRC 15155 / AMRC-C165)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
13000
-
x * ? + x * 13000, catalytic subunit, at least 2 subunits, gel filtration of enzyme precipitated by (NH4)2SO4
21000
-
x * 21000 + x * 23000, two bands, enzyme is probably a tetramer, recombinant enzyme, SDS-PAGE
23000
-
x * 21000 + x * 23000, two bands, enzyme is probably a tetramer, recombinant enzyme, SDS-PAGE
220000 - 230000
ligand-free enzyme, gel filtration and small-angle X-ray scattering analysis
250000
polyamine-bound enzyme, gel filtration and small-angle X-ray scattering analysis
270000
polyamine-bound enzyme, gel filtration and small-angle X-ray scattering analysis
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * ? + x * 13000, catalytic subunit, at least 2 subunits, gel filtration of enzyme precipitated by (NH4)2SO4
dimer
dodecamer
homodimer
tetramer
additional information
dimer
-
two dimer conformations are observed: a symmetric form with two open surface channels capable of binding substrate or cofactor, and an asymmetric form in which only one of the surface channels appears capable of binding and acetylating polyamines
dodecamer
three-dimensional structure in several ligand-free and ligand-bound structures, overview. The enzyme monomer has a mixed alpha/beta architecture
dodecamer
substrate-induced allosteric change of quaternary structure of spermidine N-acetyltransferase SpeG, overview. The enzyme possesses unique open dodecameric state exists in solution
dodecamer
-
substrate-induced allosteric change of quaternary structure of spermidine N-acetyltransferase SpeG, overview. The enzyme possesses unique open dodecameric state exists in solution; three-dimensional structure in several ligand-free and ligand-bound structures, overview. The enzyme monomer has a mixed alpha/beta architecture
-
tetramer
-
x * 21000 + x * 23000, two bands, enzyme is probably a tetramer, recombinant enzyme, SDS-PAGE
additional information
the enzyme occurs in open and closed conformations
additional information
-
the enzyme occurs in open and closed conformations
-
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
no modification
-
no posttranslational modification specific to eukaryotes is needed for enzyme activity
phosphoprotein
additional information
-
selfacetylation of Lys26 in the presence of acetyl-cCoA and in absence of substrate
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CRYSTALLIZATION/commentary
ORGANISM
UNIPROT
LITERATURE
hanging drop vapor diffusion method, crystal structure of PaiA in complex with CoA at 1.9A resolution, crystals belong to space group C222(1), with cell parameters of alpha = 39.9 A, beta = 135.8 A and gamma = 132.4 A
-
purified recombinant enzyme, sitting-drop vapour-diffusion method, mixing of 0.001 ml of 40 mg/ml protein in 10 mM HEPES-KOH pH 7.5, 50 mM CoA, 50 mM spermidine, 300 mM KCl, 0.1 mM EDTA, 6 mM 2-mercaptoethanol, 10% glycerol, 10 mM PMSF, 0.02% Brij-35, with 0.001 ml of reservoir solution containing 50 mM sodium cacodylate, pH 6.5, 9% w/v PEG 8000, 0.1 M calcium acetate, and equilibration against 0.5 ml reservoir solution, 20°C, a few days, X-ray diffraction structure determination and analysis at 2.5 A resolution
-
small angle X-ray scattering curves from two sets of a two-fold dilution series containing five sample dilutions of enzyme with and without presence of spermine
precipitation with polyethylene glycol, high resolution structures of wild-type and mutant SSAT, as the free dimer and in binary and ternary complexes with CoA, acetyl-CoA, spermine, and the inhibitor N1,N11-bis-(ethyl)-norspermine
-
three-dimensional crystal structure of SSAT with bound bisubstrate inhibitor, solved at 2.3 A resolution, hanging drop method, data and refinement statistics
SSAT in complex with coenzyme A, with and without bound spermine, hanging drop vapor diffusion method at 4°C, crystals of the binary complex between SSAT and CoA are obtained in 20% PEG 8000, 80 mM sodium acetate, 15% glycerol, 2 mM spermine, 1 mM CoA, and 85 mM sodium cacodylate, pH 6.0, 0.001 ml of the protein solution is mixed with 0.01 ml of precipitant solution containing 20% PEG 8000, 50 mM NaCl, 2 mM spermine, 1 mM coenzyme A, 15% glycerol, and 100 mM bicine buffer, pH 9.0. Crystals are obtained at pH 5.0-6.5 over a broad range of precipitant and salt concentrations. Introduction of spermine results in displacement of CoA from the enzyme active site. X-ray diffraction structure determination and analysis at 2.1-2.3 A resolution
-
molecular modeling of structure. Both spermidine and spermine should bind at unique position with high specificity
crystal structure is determined in an apo-form and in complex with its natural ligand (acetyl coenzyme A) and in complex with a product of reaction (coenzyme A) obtained by cocrystallization with spermidine
enzyme in ligand-free form or complxed with spermine or spermidine, and/or acetyl-CoA, X-ray diffraction structure determination and analysis at 1.85-2.83 A resolution, the enzyme occurs in open and closed conformations
purified enzyme, dodecameric structure in a ligand-free form in three different conformational states, open, intermediate and closed, sitting drop vapor diffusion method, for open state crystals: mixing of 400 nl of 10 mg/ml protein in 100 mM sodium chloride, 10 mM HEPES, pH 7.5, with 400 nl of reservoir solution containing 8% isopropanol and 0.1 M Tris-HCl, pH 8.5, for closed state crystals: mixing of 0.001 ml of 8.5 mg/ml protein in 500 mM sodium chloride, 5 mM 2-mercaptoethanol, 10 mM Tris-HCl, pH 8.3, with 0.001 ml of reservoir solution that contains 0.05 M ammonium sulfate, 0.1 M tri-sodium citrate and 15% polyethylene glycol 8000, and for intermediate state crystals: 0.001 ml of 8.5 mg/ml protein in 500 mM sodium chloride, 5 mM 2-mercaptoethanol, 10 mM Tris-HCl, pH 8.3, and 0.001 ml of reservoir solution containing 0.01 M calcium chloride, 20% methanol, and 0.1 M Tris-HCl, pH 8.5, 19°C, X-ray diffraction structure determination and analysis at 2.38-2.88 A reolution, molecular replacement. All structures are crystallized in C2 space group symmetry and contain six monomers in the asymmetric unit cell. Two hexamers related by crystallographic 2fold symmetry form the SpeG dodecamer. The open and intermediate states have a unique open dodecameric ring
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
L156F
-
mutant enzyme shows about 20fold reduced activity and over 70fold reduced activation by the polyamine analogue N1,N11-bis(ethyl)norspermine compared to the wild-type enzyme, expression of the mutant enzymes decreases cellular sensitivity to N1,N11-bis(ethyl)norspermine
E152Q
-
mutation disrupts binding of stabilizing N1,N12-bis(ethyl)spermine to enzyme
E171Q
-
mutation results in a marked stabilization of enzyme, due to the lack of formation of high-molecular-mass complexes with ubiquitin
K111R
-
mutant with the same activity as wild-type enzyme, but reduced half-life
K141R
-
mutant with 35% of activity of wild-type enzyme, increased Km for spermidine and reduced half-life
K87R
-
mutant with 70% of activity of wild-type enzyme, but significantly longer half-life, suggesting that Lys-87 may be the preferred site for ubiquination
R101K
site-directed mutagenesis of SSAT1 protein, ability to promote hypoxia-inducible factor-1 (HIF-1alpha) degradation reduced
S82D/T83A