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Information on EC 2.3.1.286 - protein acetyllysine N-acetyltransferase and Organism(s) Saccharomyces cerevisiae and UniProt Accession P53686

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IUBMB Comments
The enzyme, found in all domains of life, is involved in gene regulation by deacetylating proteins. Some of the 2''-O-acetyl-ADP-D-ribose converts non-enzymically to 3''-O-acetyl-ADP-D-ribose.
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Saccharomyces cerevisiae
UNIPROT: P53686
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The taxonomic range for the selected organisms is: Saccharomyces cerevisiae
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
sirt1, sirt3, sirtuin, sirt2, sirtuin 1, sirtuin 3, sir2p, silent information regulator 2, sir2alpha, nad-dependent histone deacetylase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
NAD+-dependent protein deacetylase
-
-
-
-
NAD-dependent protein deacetylase
-
-
protein lysine deacetylase
-
-
-
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silent information regulator 2
-
-
PATHWAY SOURCE
PATHWAYS
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-
SYSTEMATIC NAME
IUBMB Comments
[protein]-N6-acetyl-L-lysine:NAD+ N-acetyltransferase (NAD+-hydrolysing; 2''-O-acetyl-ADP-D-ribose-forming)
The enzyme, found in all domains of life, is involved in gene regulation by deacetylating proteins. Some of the 2''-O-acetyl-ADP-D-ribose converts non-enzymically to 3''-O-acetyl-ADP-D-ribose.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
fluorogenic acetyl-L-lysine + NAD+ + H2O
?
show the reaction diagram
-
-
-
?
[histone H4]-N6-acetyl-L-lysine16 + NAD+ + H2O
[histone H4]-L-lysine16 + 2''-O-acetyl-ADP-D-ribose + nicotinamide
show the reaction diagram
-
-
-
?
[protein]-N6-acetyl-L-lysine + NAD+ + H2O
[protein]-L-lysine + 2''-O-acetyl-ADP-D-ribose + nicotinamide
show the reaction diagram
overall reaction
-
-
?
acetyl-cytochrome c + NAD+ + H2O
?
show the reaction diagram
-
the enzyme does not deacetylate native acetyl-cytochrome c but does deacetylate the heat-denatured substrate
-
-
?
acetyl-poly-L-lysine + NAD+ + H2O
?
show the reaction diagram
-
-
-
-
?
AGG(AcK)GG(AcK)GMG(AcK)VGA(AcK)RHSC + NAD+ + H2O
AGG(AcK)GG(AcK)GMG(AcK)VGAKRHSC + 2''-O-acetyl-ADP-D-ribose + nicotinamide
show the reaction diagram
-
tetraacetylated histone-H4 N-terminal tail peptide
-
-
?
ARTKQTAR(AcK)STGG(AcK)APRKQLC + NAD+ + H2O
ARTKQTARKSTGGKAPRKQLC + 2''-O-acetyl-ADP-D-ribose + nicotinamide
show the reaction diagram
-
diacetyl ated histone-H3 N-terminal tail peptide
-
-
?
KKGQSTSRHKKAcLMFKTEG + NAD+ + H2O
KKGQSTSRHKKLMFKTEG + 2''-O-acetyl-ADP-D-ribose + nicotinamide
show the reaction diagram
-
-
-
-
r
KKGQSTSRHKLMFKTEG + 2''-O-acetyl-ADP-D-ribose + nicotinamide
KKGQSTSRHKKAcLMFKTEG + NAD+ + H2O
show the reaction diagram
-
-
-
-
r
KSTGGAcKAPRKQ + NAD+ + H2O
KSTGGKAPRKQ + 2''-O-acetyl-ADP-D-ribose + nicotinamide
show the reaction diagram
-
-
-
-
?
KSTGGK(Ac)APRKQ + beta-2'-deoxy-2'-fluororibo-NAD+ + H2O
?
show the reaction diagram
-
the rates with beta-2'-deoxy-2'-fluororibo-NAD+ are about 200fold slower than the exchange rates determined with NAD+ under similar conditions
-
-
?
KSTGGK(Ac)APRKQ + NAD+ + H2O
KSTGGKAPRKQ + 2''-O-acetyl-ADP-D-ribose + nicotinamide
show the reaction diagram
-
an 11-mer histone H3 peptide
-
-
?
[histone H2B]-N6-acetyl-L-lysine + NAD+ + H2O
[histone H2B]-L-lysine + 2''-O-acetyl-ADP-D-ribose + nicotinamide
show the reaction diagram
-
-
-
-
?
[histone H2]-N6-acetyl-L-lysine + NAD+ + H2O
[histone H2]-L-lysine + 2''-O-acetyl-ADP-D-ribose + nicotinamide
show the reaction diagram
-
-
-
-
?
[histone H3]-N6-acetyl-L-lysine + NAD+ + H2O
[histone H3]-L-lysine + 2''-O-acetyl-ADP-D-ribose + nicotinamide
show the reaction diagram
-
-
-
-
?
[histone H4]-N6-acetyl-L-lysine + NAD+ + H2O
[histone H4]-L-lysine + 2''-O-acetyl-ADP-D-ribose + nicotinamide
show the reaction diagram
-
-
-
-
?
[histone H4]-N6-acetyl-L-lysine16 + NAD+ + H2O
[histone H4]-L-lysine16 + 2''-O-acetyl-ADP-D-ribose + nicotinamide
show the reaction diagram
-
overall reaction
-
-
?
[protein]-L-lysine + 2''-O-acetyl-ADP-D-ribose + nicotinamide
[protein]-N6-acetyl-L-lysine + NAD+ + H2O
show the reaction diagram
-
-
-
-
r
[protein]-N6-acetyl-L-lysine + NAD+
[protein]-N6-[1,1-(5-adenosylyl-alpha-D-ribose-1,2-di-O-yl)ethyl]-L-lysine + nicotinamide
show the reaction diagram
-
-
-
-
?
[protein]-N6-acetyl-L-lysine + NAD+ + H2O
[protein]-L-lysine + 2''-O-acetyl-ADP-D-ribose + nicotinamide
show the reaction diagram
[protein]-N6-[1,1-(5-adenosylyl-alpha-D-ribose-1,2-di-O-yl)ethyl]-L-lysine + H2O
[protein]-L-lysine + 2''-O-acetyl-ADP-D-ribose
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
the enzyme is specific for acetyl-lysine within proteins. It does not deacetylate small polycations such as acetyl-spermine or acetyl-protamine or acetylated amino termini of proteins. Furthermore, the enzyme displays conformational rather than sequence specificity, preferentially deacetylating acetyl-lysine within unstructured regions of proteins
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
[protein]-N6-acetyl-L-lysine + NAD+ + H2O
[protein]-L-lysine + 2''-O-acetyl-ADP-D-ribose + nicotinamide
show the reaction diagram
overall reaction
-
-
?
[protein]-L-lysine + 2''-O-acetyl-ADP-D-ribose + nicotinamide
[protein]-N6-acetyl-L-lysine + NAD+ + H2O
show the reaction diagram
-
-
-
-
r
[protein]-N6-acetyl-L-lysine + NAD+
[protein]-N6-[1,1-(5-adenosylyl-alpha-D-ribose-1,2-di-O-yl)ethyl]-L-lysine + nicotinamide
show the reaction diagram
-
-
-
-
?
[protein]-N6-acetyl-L-lysine + NAD+ + H2O
[protein]-L-lysine + 2''-O-acetyl-ADP-D-ribose + nicotinamide
show the reaction diagram
[protein]-N6-[1,1-(5-adenosylyl-alpha-D-ribose-1,2-di-O-yl)ethyl]-L-lysine + H2O
[protein]-L-lysine + 2''-O-acetyl-ADP-D-ribose
show the reaction diagram
-
-
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
nicotinamide
noncompetitive inhibitor
3-acetylpyridine
-
16.8% inhibition at 30 mM
3-bromopyridine
-
19.1% inhibition at 30 mM
3-chloropyridine
-
9% inhibition at 30 mM
3-fluoropyridine
-
less than 2% inhibition at 30 mM
3-hydroxypyridine
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83.9% inhibition at 15 mM
3-methoxypyridine
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10.8% inhibition at 30 mM
3-pyridine-carboxyaldehyde
-
10.6% inhibition at 30 mM
3-Pyridinemethanol
-
22.5% inhibition at 30 mM
acetyl-protamine
-
-
-
Isonicotinamide
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5% inhibition at 42 mM
nicotinamide
nicotinic acid
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18.3% inhibition at 15 mM
poly-L-arginine
-
-
Pyrazinamide
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1% inhibition at 5 mM
Pyridine
-
6.4% inhibition at 30 mM
Thionicotinamide
[histone H3]-difluoroacetyl-L-lysine
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-
-
[histone H3]-monofluoroacetyl-L-lysine
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-
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[histone H3]-thioacetyl-L-lysine
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most potent inhibitor
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[histone H3]-trifluoroacetyl-L-lysine
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additional information
-
not inhibited by benzamide
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0161 - 0.4535
NAD+
0.037 - 0.16
nicotinamide
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.15 - 2.2
KSTGGAcKAPRKQ
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.298
nicotinamide
-
at pH 7.5 and 37°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.132
[histone H3]-difluoroacetyl-L-lysine
Saccharomyces cerevisiae
-
at pH 7.5 and 25°C
-
0.133
[histone H3]-monofluoroacetyl-L-lysine
Saccharomyces cerevisiae
-
at pH 7.5 and 25°C
-
0.00102
[histone H3]-thioacetyl-L-lysine
Saccharomyces cerevisiae
-
at pH 7.5 and 25°C
-
0.061
[histone H3]-trifluoroacetyl-L-lysine
Saccharomyces cerevisiae
-
at pH 7.5 and 25°C
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme in complex with its acetyl-lysine 16 histone H4 substrate, nicotinamide and the reaction intermediate analog ADP-HPD, vapor diffusion method, using 2.0 M (NH4)2SO4, 100 mM Na citrate, pH 5.6, 200 mM K/Na tartrate or 2.0 M (NH4)2SO4 and 100 mM Na citrate, pH 5.5
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D118N
the mutant retains approximately 13% of the activity of the wild type protein
I117F
the mutant is nearly as active as the wild type protein (about 75% activity)
I117L
the mutant retains approximately 25% of the activity of the wild type protein
I117V
the mutant is nearly as active as the wild type protein (about 65% activity)
H135A
-
the kcat/Km profile for the mutant exhibits no pH dependence over the range tested (pH 5.4-9.4), with kcat/Km values 2 orders of magnitude lower than wild type at high pH values
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
His bind affinity resin column chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Sauve, A.A.; Schramm, V.L.
Sir2 regulation by nicotinamide results from switching between base exchange and deacetylation chemistry
Biochemistry
42
9249-9256
2003
Archaeoglobus fulgidus, Saccharomyces cerevisiae, Mus musculus
Manually annotated by BRENDA team
Smith, B.C.; Denu, J.M.
Sir2 protein deacetylases evidence for chemical intermediates and functions of a conserved histidine
Biochemistry
45
272-282
2006
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Smith, B.C.; Denu, J.M.
Mechanism-based inhibition of Sir2 deacetylases by thioacetyl-lysine peptide
Biochemistry
46
14478-14486
2007
Saccharomyces cerevisiae, Homo sapiens
Manually annotated by BRENDA team
Sauve, A.A.; Schramm, V.L.
SIR2 the biochemical mechanism of NAD+-dependent protein deacetylation and ADP-ribosyl enzyme intermediates
Curr. Med. Chem.
11
807-826
2004
Saccharomyces cerevisiae
Manually annotated by BRENDA team
North, B.J.; Verdin, E.
Sirtuins Sir2-related NAD-dependent protein deacetylases
Genome Biol.
5
224
2004
Archaeoglobus fulgidus (O28597), Saccharomyces cerevisiae (P53686), Homo sapiens (Q8IXJ6), Homo sapiens, Archaeoglobus fulgidus ATCC 49558 (O28597)
Manually annotated by BRENDA team
Jackson, M.D.; Schmidt, M.T.; Oppenheimer, N.J.; Denu, J.M.
Mechanism of nicotinamide inhibition and transglycosidation by Sir2 histone/protein deacetylases
J. Biol. Chem.
278
50985-50998
2003
Saccharomyces cerevisiae, Homo sapiens
Manually annotated by BRENDA team
Khan, A.N.; Lewis, P.N.
Unstructured conformations are a substrate requirement for the Sir2 family of NAD-dependent protein deacetylases
J. Biol. Chem.
280
36073-36078
2005
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Kang, W.K.; Devare, M.; Kim, J.Y.
HST1 increases replicative lifespan of a sir2DELTA mutant in the absence of PDE2 in Saccharomyces cerevisiae
J. Microbiol.
55
123-129
2017
Saccharomyces cerevisiae, Saccharomyces cerevisiae BY4741
Manually annotated by BRENDA team
Sanders, B.D.; Zhao, K.; Slama, J.T.; Marmorstein, R.
Structural basis for nicotinamide inhibition and base exchange in Sir2 enzymes
Mol. Cell
25
463-472
2007
Saccharomyces cerevisiae (P53686)
Manually annotated by BRENDA team
Swygert, S.G.; Senapati, S.; Bolukbasi, M.F.; Wolfe, S.A.; Lindsay, S.; Peterson, C.L.
SIR proteins create compact heterochromatin fibers
Proc. Natl. Acad. Sci. USA
115
12447-12452
2018
Saccharomyces cerevisiae
Manually annotated by BRENDA team
Landry, J.; Sutton, A.; Tafrov, S.T.; Heller, R.C.; Stebbins, J.; Pillus, L.; Sternglanz, R.
The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases
Proc. Natl. Acad. Sci. USA
97
5807-5811
2000
Saccharomyces cerevisiae
Manually annotated by BRENDA team