Information on EC 2.4.2.B15 - protein-lysine deacylase (NAD+)

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The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
2.4.2.B15
preliminary BRENDA-supplied EC number
RECOMMENDED NAME
GeneOntology No.
protein-lysine deacylase (NAD+)
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
NAD+ + [protein]-N6-acyl-L-lysine = nicotinamide + [protein]-L-lysine + 2'-O-acyl-ADP-ribose
show the reaction diagram
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
NAD+ + N2-benzyloxycarbonyl-N6-succinyl-L-lysine-7-amido-4-methylcoumarin
nicotinamide + N2-benzyloxycarbonyl-L-lysine-7-amido-4-methylcoumarin + 2'-O-succinyl-ADP ribose
show the reaction diagram
i.e. 3-[(5-[[(benzyloxy)carbonyl]amino]-5-[(4-methyl-2-oxo-2H-chromen-7-yl)carbamoyl]pentyl)carbamoyl]-propanoic acid
-
-
?
NAD+ + N2-benzyloxycarbonyl-N6-succinyl-L-lysine-7-amido-4-methylcoumarin
nicotinamide + N2-benzyloxycarbonyl-L-lysine-7-amido-4-methylcoumarin + 2'-O-succinyl-ADP-ribose
show the reaction diagram
i.e. 3-[(5-[[(benzyloxy)carbonyl]amino]-5-[(4-methyl-2-oxo-2H-chromen-7-yl)carbamoyl]pentyl)carbamoyl]-propanoic acid
-
-
?
NAD+ + QTAR(N6-acetyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
acetylated histone H3 peptide
-
-
?
NAD+ + QTAR(N6-butyryl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-butyryl-ADP-ribose
show the reaction diagram
NAD+ + QTAR(N6-crotonyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-crotonyl-ADP-ribose
show the reaction diagram
NAD+ + QTAR(N6-decanoyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-decanoyl-ADP-ribose
show the reaction diagram
NAD+ + QTAR(N6-dodecanoyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-dodecanoyl-ADP-ribose
show the reaction diagram
NAD+ + QTAR(N6-hexanoyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-hexanoyl-ADP-ribose
show the reaction diagram
-
hexanoylated histone H3 peptide
-
-
?
NAD+ + QTAR(N6-hexanoyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-propionyl-ADP-ribose
show the reaction diagram
NAD+ + QTAR(N6-myristoyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-decanoyl-ADP-ribose
show the reaction diagram
NAD+ + QTAR(N6-myristoyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-myristoyl-ADP-ribose
show the reaction diagram
-
myristoylated histone H3 peptide, about 45% compared to the activity with the acetylated or hexanoylated peptide
-
-
?
NAD+ + QTAR(N6-octanoyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-octanoyl-ADP-ribose
show the reaction diagram
NAD+ + QTAR(N6-palmitoyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-palmitoyl-ADP-ribose
show the reaction diagram
-
myristoylated histone H3 peptide, about 30% compared to the activity with the acetylated or hexanoylated peptide
-
-
?
NAD+ + QTAR(N6-propionyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-propionyl-ADP-ribose
show the reaction diagram
NAD+ + QTAR(N6-succinyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-succinyl-ADP-ribose
show the reaction diagram
-
succinylated histone H3 peptide, about 10% compared to the activity with the acetylated peptide
-
-
?
NAD+ + TRSG(N6-acetyl)KVMR
nicotinamide + TRSGKVMR + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
peptide based on an acetyl-CoA synthetase 2 acetylation site
-
-
?
NAD+ + TRSG(N6-acetyl)KVMRRLLR
nicotinamide + TRSGKVMRRLLR + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
acetylated substrate peptide based on the sequence of acetyl-coenzyme A synthetase 2
-
-
?
NAD+ + [alpha-tubulin peptide]-N6-acetyl-L-lysine
nicotinamide + [alpha-tubulin peptide]-L-lysine + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
-
-
-
?
NAD+ + [alpha-tubulin]-N6-acetyl-L-lysine40
nicotinamide + [alpha-tubulin]-L-lysine40 + 2'-O-acetyl-ADP ribose
show the reaction diagram
-
-
-
-
?
NAD+ + [chicken erythrocyte histone]-N6-acetyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP ribose
show the reaction diagram
-
-
-
-
?
NAD+ + [DNA repair factor Ku70]-N6-acetyl-L-lysine382
nicotinamide + [DNA repair factor Ku70]-L-lysine382 + 2'-O-acetyl-ADP-ribose
show the reaction diagram
NAD+ + [Fluor de Lys]-N6-acetyl-L-lysine
nicotinamide + [Fluor de Lys]-L-lysine + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
Fluor de Lys is a fluorogenic, acetylated peptide substrate for human sirtuin 1, based on residues 379-382 of p53 (Arg-His-Lys-Lys(Ac)), a site of regulatory acetylation by the p300 and CBP acetyltransferases
-
-
?
NAD+ + [glutamate dehydrogenase]-N6-acetyl-L-lysine
nicotinamide + [glutamate dehydrogenase]-L-lysine + 2'-O-acetyl-ADP-ribose
show the reaction diagram
NAD+ + [histone H3]-N6-acetyl-L-lysine9
nicotinamide + [histone H3]-L-lysine9 + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
deacetylated at high concentrations of enzyme
-
-
?
NAD+ + [histone H4]-N6-acetyl-L-lysine16
nicotinamide + [histone H4]-L-lysine16 + 2'-O-acetyl-ADP-ribose
show the reaction diagram
NAD+ + [histone H4]-N6-acetyl-L-lysine8
nicotinamide + [histone H4]-L-lysine8 + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
deacetylated at high concentrations of enzyme
-
-
?
NAD+ + [isocitrate dehydrogenase 2]-N6-acetyl-L-lysine
nicotinamide + [isocitrate dehydrogenase 2]-L-lysine + 2'-O-acetyl-ADP-ribose
show the reaction diagram
NAD+ + [isocitrate dehydrogenase 2]-N6-acetyl-L-lysine413
nicotinamide + [isocitrate dehydrogenase 2]-L-lysine413 + 2'-O-acetyl-ADP-ribose
show the reaction diagram
NAD+ + [nuclear receptor LXRalpha]-N6-acetyl-L-lysine432
nicotinamide + [nuclear receptor LXRalpha]-L-lysine432 + 2'-O-acetyl-ADP ribose
show the reaction diagram
-
-
-
-
?
NAD+ + [nuclear receptor LXRbeta]-N6-acetyl-L-lysine433
nicotinamide + [nuclear receptor LXRbeta]-L-lysine433 + 2'-O-acetyl-ADP ribose
show the reaction diagram
-
-
-
-
?
NAD+ + [nuclear receptor LXR]-N6-acetyl-L-lysine
nicotinamide + [nuclear receptor LXR]-L-lysine + 2'-O-acetyl-ADP ribose
show the reaction diagram
-
SIRT1 positively regulates liver X receptors (LXRs) by deacetylation at lysine. Deacetylation of liver X receptors (LXRs) by SIRT1 may be a mechanism that affects atherosclerosis and other agingassociated diseases
-
-
?
NAD+ + [p53 protein]-N6-acetyl-L-lysine
nicotinamide + [p53 protein]-L-lysine + 2'-O-acetyl-ADP-ribose
show the reaction diagram
NAD+ + [p53 protein]-N6-acetyl-L-lysine382
nicotinamide + [p53 protein]-L-lysine382 + 2'-O-acetyl-ADP ribose
show the reaction diagram
NAD+ + [PER2 protein]-N6-acetyl-L-lysine
nicotinamide + [PER2 protein]-L-lysine + 2'-O-acetyl-ADP-ribose
show the reaction diagram
NAD+ + [protein]-N6-succinyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
show the reaction diagram
-
-
-
-
?
NAD+ + [SREBP-1c]-N6-acetyl-L-lysine
nicotinamide + [SREBP-1c]-L-lysine + 2'-O-acetyl-ADP ribose
show the reaction diagram
NAD+ + [thymine DNA glycosylase]-N6-acetyl-L-lysine
nicotinamide + [thymine DNA glycosylase]-L-lysine + 2'-O-acetyl-ADP-ribose
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
NAD+ + [chicken erythrocyte histone]-N6-acetyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP ribose
show the reaction diagram
-
-
-
-
?
NAD+ + [DNA repair factor Ku70]-N6-acetyl-L-lysine382
nicotinamide + [DNA repair factor Ku70]-L-lysine382 + 2'-O-acetyl-ADP-ribose
show the reaction diagram
NAD+ + [glutamate dehydrogenase]-N6-acetyl-L-lysine
nicotinamide + [glutamate dehydrogenase]-L-lysine + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
Sirt3 can deacetylate and thereby activate a central metabolic regulator in the mitochondrial matrix, glutamate dehydrogenase
-
-
?
NAD+ + [histone H4]-N6-acetyl-L-lysine16
nicotinamide + [histone H4]-L-lysine16 + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
the deacetylation of [histone H4]-N6-acetyl-L-lysine16 may be pivotal to the formation of condensed chromatin
-
-
?
NAD+ + [isocitrate dehydrogenase 2]-N6-acetyl-L-lysine
nicotinamide + [isocitrate dehydrogenase 2]-L-lysine + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
Sirt3 can deacetylate and activate isocitrate dehydrogenase 2, an enzyme that promotes regeneration of antioxidants and catalyzes a key regulation point of the citric acid cycle
-
-
?
NAD+ + [isocitrate dehydrogenase 2]-N6-acetyl-L-lysine413
nicotinamide + [isocitrate dehydrogenase 2]-L-lysine413 + 2'-O-acetyl-ADP-ribose
show the reaction diagram
Q8R104
acetylation of Lys413 decreases catalysis and SIRT3 reactivates isocitrate dehydrogenase 2 upon deacetylation
-
-
?
NAD+ + [nuclear receptor LXR]-N6-acetyl-L-lysine
nicotinamide + [nuclear receptor LXR]-L-lysine + 2'-O-acetyl-ADP ribose
show the reaction diagram
-
SIRT1 positively regulates liver X receptors (LXRs) by deacetylation at lysine. Deacetylation of liver X receptors (LXRs) by SIRT1 may be a mechanism that affects atherosclerosis and other agingassociated diseases
-
-
?
NAD+ + [p53 protein]-N6-acetyl-L-lysine
nicotinamide + [p53 protein]-L-lysine + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
SIRT1 deacetylase is a negative regulator of p53 function capable of modulating cellular senescence
-
-
?
NAD+ + [p53 protein]-N6-acetyl-L-lysine382
nicotinamide + [p53 protein]-L-lysine382 + 2'-O-acetyl-ADP ribose
show the reaction diagram
-
Sir2 is involved in the regulation of p53 function via deacetylation
-
-
?
NAD+ + [PER2 protein]-N6-acetyl-L-lysine
nicotinamide + [PER2 protein]-L-lysine + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
SIRT1 regulates circadian clock gene expression through PER2 deacetylation
-
-
?
NAD+ + [protein]-N6-succinyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
show the reaction diagram
-
-
-
-
?
NAD+ + [SREBP-1c]-N6-acetyl-L-lysine
nicotinamide + [SREBP-1c]-L-lysine + 2'-O-acetyl-ADP ribose
show the reaction diagram
Q923E4
SREBP-1c is a key lipogenic activator. Deacetylation of SREBP-1c by SIRT1 inhibits SREBP-1c activity by decreasing its stability and its association with its lipogenic target gene promoters
-
-
?
NAD+ + [thymine DNA glycosylase]-N6-acetyl-L-lysine
nicotinamide + [thymine DNA glycosylase]-L-lysine + 2'-O-acetyl-ADP-ribose
show the reaction diagram
-
deacetylation and stimulation of the thymine DNA glycosylase activity by SIRT1 enhances DNA demethylation
-
-
?
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(4R)-1-(tert-butoxycarbonyl)-4-hydroxyprolyl-N-benzyl-N6-ethanethioyl-L-lysinamide
-
0.05 mM, 83.4% inhibition
(4R)-1-(tert-butoxycarbonyl)-N-[(2S)-6-(ethanethioylamino)-1-oxo-1-[(2-oxo-2-phenylethyl)amino]hexan-2-yl]-4-hydroxyprolinamide
-
0.05 mM, 97.1% inhibition
(4R)-4-hydroxyprolyl-N-benzyl-N6-ethanethioyl-L-lysinamide
-
0.05 mM, 89.3% inhibition
(4R)-N-[(2S)-6-(ethanethioylamino)-1-oxo-1-[(2-oxo-2-phenylethyl)amino]hexan-2-yl]-4-hydroxyprolinamide
-
0.05 mM, 96.8% inhibition
(5E)-1-ethyl-5-(1H-indol-3-ylmethylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
; 10% inhibition at 0.05 mM
-
(5E)-5-(1H-indol-3-ylmethylidene)-1-methyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
; 17% inhibition at 0.05 mM; 20% inhibition at 0.05 mM
-
(5E)-5-[4-(benzyloxy)benzylidene]-1-(prop-2-en-1-yl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
; 13% inhibition at 0.05 mM
-
(5E)-5-[4-(benzyloxy)benzylidene]-1-ethyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
25% inhibition at 0.05 mM
-
(5E)-5-[4-(benzyloxy)benzylidene]-1-methyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
22% inhibition at 0.05 mM
-
(5E)-5-[[5-(2,3-dichlorophenyl)furan-2-yl]methylidene]-1-(prop-2-en-1-yl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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41% inhibition at 0.05 mM
-
1-(tert-butoxycarbonyl)prolyl-N-benzyl-N6-ethanethioyl-L-lysinamide
-
0.05 mM, 93.7% inhibition
2-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-(4-cyano-2-fluorophenyl)isonicotinamide
-
highly selective inhibitor for SIRT2, low inhibition of SIRT1 and SIRT3
2-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-(4-cyanophenyl)isonicotinamide
-
selective inhibitor for SIRT2, low inhibition of SIRT1 and SIRT3
2-[1-[3-(amidinothio)propyl]-1H-indol-3-yl]-3-(1-methylindol-3-yl)maleimide methanesulfonate
-
i.e. Ro 31-8220; i.e. Ro 31-8220; i.e. Ro 31-8220
-
3-((2-methoxynaphthalen-1-yl)methyl)-7-((2-methylbenzyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
-
-
3-((2-methoxynaphthalen-1-yl)methyl)-7-((pyridin-3-ylmethyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
-
i.e. ICL-SIRT078, a substrate-competitive SIRT2 inhibitor with more than 50fold selectivity against SIRT1, 3 and 5. Treatment of MCF-7 breast cancer cells with ICL-SIRT078 results in hyperacetylation of alpha-tubulin, an established SIRT2 biomarker, at doses comparable with the biochemical IC50 data, while suppressing MCF-7 proliferation at higher concentrations
-
3-((2-methoxynaphthalen-1-yl)methyl)-7-((thiophen-2-ylmethyl)-amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
-
-
3-((2-methoxynaphthalen-1-yl)methyl)-7-(neopentylamino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
-
-
3-(azepan-1-ylsulfonyl)-N-(3-nitrophenyl)benzamide
-
highly selective inhibitor for SIRT2, low inhibition of SIRT1 and SIRT3
3-(N-(4-acetylphenyl)-N-methylsulfamoyl)-N-(4-chlorophenyl)benzamide
-
highly selective inhibitor for SIRT2, no inhibition of SIRT1, low inhibition of and SIRT3
3-(N-(4-acetylphenyl)-N-methylsulfamoyl)-N-(4-cyanophenyl)benzamide
-
highly selective inhibitor for SIRT2, low inhibition of SIRT1 and SIRT3
3-(N-(4-acetylphenyl)-N-methylsulfamoyl)-N-(5-chloropyridin-2-yl)benzamide
-
highly selective inhibitor for SIRT2, low inhibition of SIRT1, no inhibition of and SIRT3
3-(N-(4-bromophenyl)-N-methylsulfamoyl)-N-(4-chloro-2-fluorophenyl)-N-methylbenzamide
-
highly selective inhibitor for SIRT2, low inhibition of SIRT1 and SIRT3
3-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-(4-(methylsulfinyl)phenyl)benzamide
-
highly selective inhibitor for SIRT2, no inhibition of SIRT1, low inhibition of and SIRT3
3-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-(4-(methylsulfonyl)phenyl)benzamide
-
highly selective inhibitor for SIRT2, low inhibition of SIRT1 and SIRT3
3-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-(4-cyano-2-fluorophenyl)benzamide
-
highly selective inhibitor for SIRT2, low inhibition of SIRT1 and SIRT3
3-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-(4-cyanophenyl)benzamide
-
highly selective inhibitor for SIRT2, low inhibition of SIRT1, no inhibition of and SIRT3
3-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-(5-cyanopyridin-2-yl)benzamide
-
highly selective inhibitor for SIRT2, low inhibition of SIRT1, no inhibition of and SIRT3
3-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-(5-fluoropyridin-2-yl)benzamide
-
highly selective inhibitor for SIRT2, no inhibition of SIRT1 and SIRT3
3-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-(6-chloropyridazin-3-yl)benzamide
-
highly selective inhibitor for SIRT2, low inhibition of SIRT1
3-(N-(5-chloropyridin-2-yl)-N-methylsulfamoyl)-N-(4-cyanophenyl)benzamide
-
highly selective inhibitor for SIRT2, low inhibition of SIRT1 and SIRT3
4-bromo-N-(3-(N-methyl-N-(4-(methylsulfonyl)phenyl)sulfamoyl)phenyl)benzamide
-
selective inhibitor for SIRT2, low inhibition of SIRT1 and SIRT3
5-(1H-indol-3-ylmethylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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14% inhibition at 0.05 mM
-
5-(biphenyl-4-ylmethylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
-
-
5-[(1-benzyl-1H-indol-3-yl)methylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
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20% inhibition at 0.05 mM
-
5-[(6-methoxynaphthalen-1-yl)methylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
-
-
5-[4-(benzyloxy)benzylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
-
-
5-[4-(propan-2-yl)benzylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
13% inhibition at 0.05 mM
-
5-[4-[(2-chlorobenzyl)oxy]-3-methoxybenzylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
-
-
5-[4-[(4-bromobenzyl)oxy]benzylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
-
-
5-[[5-(2,3-dichlorophenyl)furan-2-yl]methylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
30% inhibition at 0.05 mM
-
6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide
7-((3-fluorobenzyl)amino)-3-((2-methoxynaphthalen-1-yl)methyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
-
-
7-((3-methoxybenzyl)amino)-3-((2-methoxynaphthalen-1-yl)-methyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
-
-
-
7-(benzylamino)-3-((2-methoxynaphthalen-1-yl)methyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
-
-
cambinol
-
;
-
fisetin
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-
Isonicotinamide
-
weak competitive inhibitor of hSIRT3 with respect to NAD+ in vitro; weak inhibitor
macrocyclic peptide inhibitor S2iL5
-
the inhibitor binds to the active site of SIRT2 through extensive interactions. The inhibitor induces an open-to-closed domain movement and a helix-to-coil transition in a SIRT2-specific region
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methyl N2-(tert-butoxycarbonyl)-N6-ethanethioyl-L-lysyl-D-alaninate
-
0.05 mM, 81.3% inhibition
N-(3-(N-(4-chlorophenyl)-N-methylsulfamoyl)phenyl)-4-cyanobenzamide
-
highly selective inhibitor for SIRT2, low inhibition of SIRT1, no inhibition of and SIRT3
N-(4-acetylphenyl)-3-(N-(4-acetylphenyl)-N-methylsulfamoyl)benzamide
-
highly selective inhibitor for SIRT2, no inhibition of SIRT1 and SIRT3
N-(4-bromo-2-fluorophenyl)-3-(N-(4-bromophenyl)-N-methylsulfamoyl)-N-methylbenzamide
-
highly selective inhibitor for SIRT2, no inhibition of SIRT1 and SIRT3
N-(4-chlorophenyl)-3-(N-methyl-N-(4-(methylsulfonyl)phenyl)sulfamoyl)benzamide
-
highly selective inhibitor for SIRT2, no inhibition of SIRT1 and SIRT3
N-(4-cyanophenyl)-3-(N-(4-(1-hydroxyethyl)phenyl)-N-methylsulfamoyl)benzamide
-
-
N-(4-cyanophenyl)-3-(N-(4-fluorophenyl)-N-methylsulfamoyl)benzamide
-
highly selective inhibitor for SIRT2, low inhibition of SIRT1 and SIRT3
N-(4-cyanophenyl)-3-(N-(4-methoxyphenyl)-N-methylsulfamoyl)benzamide
-
highly selective inhibitor for SIRT2, low inhibition of SIRT1 and SIRT3
N-(4-cyanophenyl)-3-(N-methyl-N-(4-(methylsulfonyl)phenyl)sulfamoyl)benzamide
-
highly selective inhibitor for SIRT2, low inhibition of SIRT1, no inhibition of and SIRT3
N-[(2S)-6-(ethanethioylamino)-1-oxo-1-[(2-oxo-2-phenylethyl)amino]hexan-2-yl]-5-oxoprolinamide
-
0.05 mM, 98.2% inhibition
N-[(2S)-6-(ethanethioylamino)-1-[[2-(morpholin-4-yl)ethyl]amino]-1-oxohexan-2-yl]-6-oxoheptanamide
-
0.05 mM, 61.1% inhibition
N2-(tert-butoxycarbonyl)-N6-ethanethioyl-N-[2-(4-methoxyphenyl)-2-oxoethyl]-L-lysinamide
-
0.05 mM, 95.6% inhibition
N2-(tert-butoxycarbonyl)-N6-ethanethioyl-N-[2-(morpholin-4-yl)ethyl]-L-lysinamide
-
0.05 mM, 37.5% inhibition
N2-[(benzyloxy)carbonyl]-N6-ethanethioyl-N-[2-(morpholin-4-yl)ethyl]-L-lysinamide
-
0.05 mM, 54.9% inhibition
N6-ethanethioyl-N2-(6-oxoheptanoyl)-N-(2-oxo-2-phenylethyl)-L-lysinamide
-
0.05 mM, 97.7% inhibition
nicotinamide
prolyl-N-benzyl-N6-ethanethioyl-L-lysinamide
-
0.05 mM, 94.8% inhibition
resveratrol
-
inhibits deacetylase activity
sirtinol
-
24% inhibition at 0.05 mM
-
suramin
-
;
additional information
-
no inhibition at 0.05 mM: (5E)-1-ethyl-5-(1H-indol-3-ylmethylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione; no inhibition at 0.05 mM: (5E)-5-[4-(benzyloxy)benzylidene]-1-(prop-2-en-1-yl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione; no inhibition by EX-527, HR 103 or Ro 31-8220; no inhibition by EX-527, HR 103 or Ro 31-8220; no inhibition by EX-527, HR 103 or Ro 31-8220
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00062
3-((2-methoxynaphthalen-1-yl)methyl)-7-((pyridin-3-ylmethyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
-
pH 7.5, temperature not specified in the publication
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0144
(5E)-5-[4-(benzyloxy)benzylidene]-1-ethyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
-
pH 8.0, 37C
-
0.01
(5E)-5-[4-(benzyloxy)benzylidene]-1-methyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
-
pH 8.0, 37C
-
0.0097
(5E)-5-[[5-(2,3-dichlorophenyl)furan-2-yl]methylidene]-1-(prop-2-en-1-yl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
-
pH 8.0, 37C
-
0.0102
2-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-(4-cyano-2-fluorophenyl)isonicotinamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0049
2-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-(4-cyanophenyl)isonicotinamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0008 - 0.0037
2-[1-[3-(amidinothio)propyl]-1H-indol-3-yl]-3-(1-methylindol-3-yl)maleimide methanesulfonate
-
0.0172
3-((2-methoxynaphthalen-1-yl)methyl)-7-((2-methylbenzyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
pH 7.5, temperature not specified in the publication
0.00145
3-((2-methoxynaphthalen-1-yl)methyl)-7-((pyridin-3-ylmethyl)amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
pH 7.5, temperature not specified in the publication
-
0.006
3-((2-methoxynaphthalen-1-yl)methyl)-7-((thiophen-2-ylmethyl)-amino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
pH 7.5, temperature not specified in the publication
0.00652
3-((2-methoxynaphthalen-1-yl)methyl)-7-(neopentylamino)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
pH 7.5, temperature not specified in the publication
0.0108
3-(azepan-1-ylsulfonyl)-N-(3-nitrophenyl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0068
3-(N-(4-acetylphenyl)-N-methylsulfamoyl)-N-(4-chlorophenyl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0073
3-(N-(4-acetylphenyl)-N-methylsulfamoyl)-N-(4-cyanophenyl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0132
3-(N-(4-acetylphenyl)-N-methylsulfamoyl)-N-(5-chloropyridin-2-yl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0075
3-(N-(4-bromophenyl)-N-methylsulfamoyl)-N-(4-chloro-2-fluorophenyl)-N-methylbenzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0095
3-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-(4-(methylsulfinyl)phenyl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0098
3-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-(4-(methylsulfonyl)phenyl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0066
3-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-(4-cyano-2-fluorophenyl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0061
3-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-(4-cyanophenyl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0199
3-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-(5-cyanopyridin-2-yl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0091
3-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-(5-fluoropyridin-2-yl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0156
3-(N-(4-chlorophenyl)-N-methylsulfamoyl)-N-(6-chloropyridazin-3-yl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0061
3-(N-(5-chloropyridin-2-yl)-N-methylsulfamoyl)-N-(4-cyanophenyl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0063
4-bromo-N-(3-(N-methyl-N-(4-(methylsulfonyl)phenyl)sulfamoyl)phenyl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0203
5-(1H-indol-3-ylmethylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
-
pH 8.0, 37C
-
0.0087 - 0.0403
5-(biphenyl-4-ylmethylidene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
0.116
5-[(1-benzyl-1H-indol-3-yl)methylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
-
pH 8.0, 37C
-
0.0117 - 0.0433
5-[(6-methoxynaphthalen-1-yl)methylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
0.0098 - 0.0293
5-[4-(benzyloxy)benzylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
0.0147
5-[4-(propan-2-yl)benzylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
-
pH 8.0, 37C
-
0.0075 - 0.0464
5-[4-[(2-chlorobenzyl)oxy]-3-methoxybenzylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
0.0034 - 0.0303
5-[4-[(4-bromobenzyl)oxy]benzylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
-
0.0104
5-[[5-(2,3-dichlorophenyl)furan-2-yl]methylidene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
Homo sapiens
-
pH 8.0, 37C
-
0.0001 - 0.049
6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide
0.004
7-((3-fluorobenzyl)amino)-3-((2-methoxynaphthalen-1-yl)methyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
pH 7.5, temperature not specified in the publication
0.0019
7-((3-methoxybenzyl)amino)-3-((2-methoxynaphthalen-1-yl)-methyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
pH 7.5, temperature not specified in the publication
-
0.0211
7-(benzylamino)-3-((2-methoxynaphthalen-1-yl)methyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens
-
pH 7.5, temperature not specified in the publication
0.056 - 0.059
cambinol
-
12200 - 13800
Isonicotinamide
0.0038
N-(3-(N-(4-chlorophenyl)-N-methylsulfamoyl)phenyl)-4-cyanobenzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0189
N-(4-acetylphenyl)-3-(N-(4-acetylphenyl)-N-methylsulfamoyl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0069
N-(4-bromo-2-fluorophenyl)-3-(N-(4-bromophenyl)-N-methylsulfamoyl)-N-methylbenzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0159
N-(4-chlorophenyl)-3-(N-methyl-N-(4-(methylsulfonyl)phenyl)sulfamoyl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0115
N-(4-cyanophenyl)-3-(N-(4-(1-hydroxyethyl)phenyl)-N-methylsulfamoyl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0094
N-(4-cyanophenyl)-3-(N-(4-fluorophenyl)-N-methylsulfamoyl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0096
N-(4-cyanophenyl)-3-(N-(4-methoxyphenyl)-N-methylsulfamoyl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0095
N-(4-cyanophenyl)-3-(N-methyl-N-(4-(methylsulfonyl)phenyl)sulfamoyl)benzamide
Homo sapiens
-
pH and temperature not specified in the publication
0.0012 - 0.1
nicotinamide
0.037 - 0.131
sirtinol
-
0.0003 - 0.02
suramin
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5
-
assay at
7.8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
Q96EB6
-
Manually annotated by BRENDA team
Q96EB6
-
Manually annotated by BRENDA team
Q96EB6
-
Manually annotated by BRENDA team
-
SIRT1 is located in the nucleus of cerebral cortex neurons
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
the enzyme is cytoplasmic during most of the cell cycle except in the G2/M transition and in mitosis
Manually annotated by BRENDA team
-
SIRT1 and p53 colocalize in nuclear bodies (punctate structures found in the nuclei of certain cells) upon upregulation of the promyelocytic leukemia protein
Manually annotated by BRENDA team
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
-
phosphorylation of Thr522 is an important allosteric mechanism to activate SIRT1 in response to stress. While non-phosphorylation of this residue leads to formation of less-active oligomers, phosphorylation helps to maintain the monomeric status of SIRT1, resulting in increased activity
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal structure of Sirt3 in complex with fluor-de-Lys peptide and resveratrol and crystal structure of Sirt3 in complex with fluor-de-Lys peptide and piceatannol
-
crystallization at 4C by the sitting-drop vapor diffusion method. Crystal structure of human SIRT2 in complex with a macrocyclic peptide inhibitor S2iL5, at 2.5 A resolution
-
hanging drop vapor diffusion using a 1:1 drop ratio. The 2.5 A crystal structure of the SIRT1 catalytic domain bound to NAD+ and 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide (EX527)
-
recombinant sirtuin 1 comprising residues 140747 is crystallized using the hanging-drop vapour diffusion method. The crystal diffracted to 3.4 A resolution and belong to space group P622, with unit-cell parameters a = b = 203.1, c = 625.3 A , and is estimated to contain between six and 12 molecules per asymmetric unit
-
Sirt2 is crystallized in complex with the product analog, ADP-ribose, and this crystal structure is solved at 2.3 A resolution
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
a gene encoding the C-terminally His-tagged SIRT1 catalytic domain is expressed in SF9 cells
-
expression in Escherichia coli
-
recombinant human SIRT2 (43-356) is expressed as a His-Sumo fusion protein in Escherichia coli
-
SIRT1-FL (full-length human SIRT1) is cloned in the pECE vector (clone 1791) and N-terminally truncated SIRT1 (SIRT1-NT with residues 783 deleted) cloned in the pCDNA3.1 vector. To express the FLAGtagged hSIRT1 (human SIRT1) proteins, the hSIRT1 constructs are transfected into HEK (human embryonic kidney)-293T cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
down-regulation of intratumoral and peritumoral Sirt3 are both associated with poor outcome in hepatocellular carcinoma
-
enhanced expression of SIRT5 in the cerebral tissue of calorie restriction rats compared with rats that remained fed ad libitum
-
expression of SIRT1 is induced in human cells that are treated with human serum. Insulin and insulin-like growth factor 1 (IGF-1) attenuate this response
-
expression of SIRT1 is induced in rat cells that are treated with rat serum. Insulin and insulin-like growth factor 1 (IGF-1) attenuate this response; tissues are extracted from 12-month-old rats that had either been fed ad libitum (AL) or a caloric restriction diet (CR, 60% of AL) since weaning. Compared to expression in AL animals, SIRT1 expression is higher in many tissues of the CR animals, including brain, visceral fat pads, kidney, and liver
Q96EB6
expression of SIRT3 shows a strong negative correlation with the progression of Alzheimers disease
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine