2.3.1.B43: protein-lysine desuccinylase (NAD+)
This is an abbreviated version!
For detailed information about protein-lysine desuccinylase (NAD+), go to the full flat file.
Word Map on EC 2.3.1.B43
-
2.3.1.B43
-
sirtuins
-
sirt3
-
deacetylation
-
deacetylases
-
desuccinylation
-
malonylation
-
nad-dependent
-
sirt1-7
-
glutarylation
-
diagnostics
-
medicine
-
drug development
- 2.3.1.B43
- sirtuins
- sirt3
-
deacetylation
- deacetylases
-
desuccinylation
-
malonylation
-
nad-dependent
-
sirt1-7
-
glutarylation
- diagnostics
- medicine
- drug development
Reaction
Synonyms
CobB, CobB Sir2 protein, histone desuccinylase, hSIRT5, hSIRT6, lysine desuccinylase, mitochondrial NAD+-dependent lysine deacylase, NAD+ dependent deacetylase, NAD+-dependent protein deacetylase, NAD+-dependent protein deacylase, NAD+-dependent sirtuin deacetylase, nicotinamide adenine dinucleotide-dependent protein deacetylase, Sir2Af1, SIRT5, SIRT5iso1, SIRT5iso2, SIRT5iso3, SIRT5iso4, sirtuin 5, sirtuin 5 deacylase, sirtuin 5 lysine deacylase, sirtuin deacylase, sirtuin-5, zSIRT5
ECTree
2.3.1.B43 protein-lysine desuccinylase (NAD+)Advanced search results
results (
results (Substrates Products
Substrates Products on EC 2.3.1.B43 - protein-lysine desuccinylase (NAD+)
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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
NAD+ + Ac-(N6-methylmalonyl)Lys-(7-amido-4-methylcoumarin)
nicotinamide + Ac-Lys-7-amido-4-methylcoumarin + 2'-O-methylmalonyl-ADP-ribose
-
-
-
?
NAD+ + Ac-(N6-succinyl)Lys-7-amido-4-methylcoumarin
nicotinamide + Ac-Lys-7-amido-4-methylcoumarin + 2'-O-succinyl-ADP-ribose
-
-
-
?
NAD+ + Ac-Leu-Gly-(N6-malonyl)Lys-7-amido-4-methylcoumarin
nicotinamide + Ac-Leu-Gly-Lys-7-amido-4-methylcoumarin + 2'-O-malonyl-ADP-ribose
-
-
-
?
NAD+ + Ac-Leu-Gly-(N6-succinyl)Lys-7-amido-4-methylcoumarin
nicotinamide + Ac-Leu-Gly-Lys-7-amido-4-methylcoumarin + 2'-O-succinyl-ADP-ribose
-
-
-
?
NAD+ + AFNQG(N6-malonyl)KIFK
nicotinamide + AFNQGKIFK + 2'-O-malonyl-ADP-ribose
-
-
-
?
NAD+ + AYVDDTPAEQM(N6-malonyl)KAER
nicotinamide + AYVDDTPAEQMKAER + 2'-O-malonyl-ADP-ribose
-
-
-
?
NAD+ + benzoyl-GVL(N6-acetyl)KEYGV-amide
nicotinamide + benzoyl-GVLKEYGV-amide + 2'-O-acetyl-ADP-ribose
-
-
-
?
NAD+ + benzoyl-GVL(N6-adipoyl)KEYGV-amide
nicotinamide + benzoyl-GVLKEYGV-amide + 2'-O-adipoyl-ADP-ribose
-
-
-
?
NAD+ + benzoyl-GVL(N6-glutaryl)KEYGV-amide
nicotinamide + benzoyl-GVLKEYGV-amide + 2'-O-glutaryl-ADP-ribose
-
-
-
?
NAD+ + benzoyl-GVL(N6-malonyl)KEYGV-amide
nicotinamide + benzoyl-GVLKEYGV-amide + 2'-O-malonyl-ADP-ribose
-
-
-
?
NAD+ + benzoyl-GVL(N6-oxalyl)KEYGV-amide
nicotinamide + benzoyl-GVLKEYGV-amide + 2'-O-oxalyl-ADP-ribose
-
-
-
?
NAD+ + benzoyl-GVL(N6-pimeloyl)KEYGV-amide
nicotinamide + benzoyl-GVLKEYGV-amide + 2'-O-pimeloyl-ADP-ribose
-
-
-
?
NAD+ + benzoyl-GVL(N6-suberoyl)KEYGV-amide
nicotinamide + benzoyl-GVLKEYGV-amide + 2'-O-suberoyl-ADP-ribose
-
-
-
?
NAD+ + benzoyl-GVL(N6-succinyl)KEYGV-amide
nicotinamide + benzoyl-GVLKEYGV-amide + 2'-O-succinyl-ADP-ribose
-
-
-
?
NAD+ + benzoyl-RGVL(N6-succinyl)KEYGV-amide
nicotinamide + benzoyl-RGVLKEYGV-amide + 2'-O-acetyl-ADP-ribose
carbamoyl phosphate synthetase 1 Lys527 peptide
-
-
?
NAD+ + benzyl-(N6-succinyl)Lys-7-amido-4-methylcoumarin
nicotinamide + benzyl-Lys-7-amido-4-methylcoumarin + 2'-O-succinyl-ADP-ribose
fluorogenic substrate
-
-
?
NAD+ + DSYVGDEAQSDSYVGDEAQS(N6-malonyl)KR
nicotinamide + DSYVGDEAQSDSYVGDEAQSKR + 2'-O-malonyl-ADP-ribose
-
-
-
?
NAD+ + ETGVDLT(N6-succinyl)KDNMALQR
nicotinamide + ETGVDLTKDNMALQR + 2'-O-succinyl-ADP-ribose
-
-
-
?
NAD+ + IEEELGS(N6-malonyl)KAK
nicotinamide + IEEELGSKAK + 2'-O-malonyl-ADP-ribose
-
-
-
?
NAD+ + KGLGKGGA(N6-propionyl)KRHRKW
nicotinamide + KGLGKGGAKRHRKW + 2'-O-propionyl-ADP-ribose
NAD+ + KGLGKGGA(N6-succinyl)KRHRKW
nicotinamide + KGLGKGGAKRHRKW + 2'-O-succinyl-ADP-ribose
NAD+ + KQTAR(N6-malonyl)KSTGGWW
nicotinamide + KQTARKSTGGWW + 2'-O-malonyl-ADP-ribose
histone H3K9 malonyl peptide
-
-
?
NAD+ + KQTAR(N6-succinyl)KSTGGKA
nicotinamide + KQTARKSTGGKA + 2'-O-succinyl-ADP-ribose
-
-
-
?
NAD+ + KQTAR(N6-succinyl)KSTGGWW
nicotinamide + KQTARKSTGGWW + 2'-O-succinyl-ADP-ribose
histone H3K9 succinyl peptide
-
-
?
NAD+ + KTRSG(N6-malonyl)KVMRRWW
nicotinamide + KTRSGKVMRRWW + 2'-O-malonyl-ADP-ribose
-
-
-
?
NAD+ + KTRSG(N6-succinyl)KVMRRWW
nicotinamide + KTRSGKVMRRWW + 2'-O-succinyl-ADP-ribose
ACS2 Lys628 peptide
-
-
?
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
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
acetylated histone H3 peptide, less than 10% compared to the activity with the succinylated peptide
-
-
?
NAD+ + QTAR(N6-decanoyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-decanoyl-ADP-ribose
decanoylated histone H3 peptide, about 35% compared to the activity with the succinylated peptide
-
-
?
NAD+ + QTAR(N6-dodecanoyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-dodecanoyl-ADP-ribose
dodecanoylated histone H3 peptide, about 35% compared to the activity with the succinylated peptide
-
-
?
NAD+ + QTAR(N6-hexanoyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-hexanoyl-ADP-ribose
hexanoylated histone H3 peptide, less than 10% compared to the activity with the succinylated peptide
-
-
?
NAD+ + QTAR(N6-myristoyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-myristoyl-ADP-ribose
myristoylated histone H3 peptide, about 15% compared to the activity with the succinylated peptide
-
-
?
NAD+ + QTAR(N6-octanoyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-octanoyl-ADP-ribose
octanoylated histone H3 peptide, about 30% compared to the activity with the succinylated peptide
-
-
?
NAD+ + QTAR(N6-propionyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-propionyl-ADP-ribose
propionylated histone H3 peptide, less than 10% compared to the activity with the succinylated peptide
-
-
?
NAD+ + QTAR(N6-succinyl)KSTGG
nicotinamide + QTARKSTGG + 2'-O-succinyl-ADP-ribose
succinylated histone H3 peptide
-
-
?
NAD+ + SGASE(N6-malonyl)KDIVHSGWW
nicotinamide + SGASEKDIVHSGWW + 2'-O-malonyl-ADP-ribose
-
-
-
?
NAD+ + SGASE(N6-succinyl)KDIVHSGWW
nicotinamide + SGASEKDIVHSGWW + 2'-O-succinyl-ADP-ribose
glutamate dehydrogenase Lys503 peptide
-
-
?
NAD+ + SKEYFS(N6-succinyl)KQK
nicotinamide + SKEYFSKQK + 2'-O-acetyl-ADP-ribose
-
-
-
?
NAD+ + SQG(N6-succinyl)KVLQATVV
nicotinamide + SQGKVLQATVV + 2'-O-succinyl-ADP-ribose
-
-
-
?
NAD+ + TAIG(N6-malonyl)KAGYTDK
nicotinamide + TAIGKAGYTDK + 2'-O-malonyl-ADP-ribose
-
-
-
?
NAD+ + TRSG(N6-acetyl)KVMR
nicotinamide + TRSGKVMR + 2'-O-acetyl-ADP-ribose
peptide based on an acetyl-CoA synthetase 2 acetylation site
-
-
?
NAD+ + VLLPEYGGT(N6-succinyl)KVVLDDK
nicotinamide + VLLPEYGGTKVVLDDK + 2'-O-succinyl-ADP-ribose
-
-
-
?
NAD+ + [acetyl-coenzyme A synthetase]-N6-acetyl-L-lysine609
nicotinamide + [acetyl-coenzyme A synthetase]-L-lysine609 + 2'-O-acetyl-ADP-ribose
NAD+ + [ATP synthase]-N6-succinyl-L-lysine
nicotinamide + [ATP synthase]-L-lysine + 2'-O-succinyl-ADP-ribose
NAD+ + [bovine serum albumin]-N6-acetyl-L-lysine
nicotinamide + [bovine serum albumin]-L-lysine + 2'-O-acetyl-ADP-ribose
crystallographic evidence is provided that 2'-O-acetyl ADP-ribose is a final product in the Sir2 reaction. A revised mechanism for catalysis based on the structural and functional characterization of Sir2 mutants is proposed. In this mechanism, the activation of the 2'-OH of nicotinamide ribose by His-116 is essential for the hydrolysis of the acetyl groups from N-acetyl lysine. The conserved Ser-24 and Asp-101 participate in the stabilization of local structure for NAD binding rather than direct involvement in catalysis
-
-
?
NAD+ + [carbamoyl phosphate synthase 1]-N6-acetyl-L-lysine
nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-acetyl-ADP ribose
NAD+ + [carbamoyl phosphate synthase 1]-N6-acetyl-L-lysine
nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-acetyl-ADP-ribose
NAD+ + [carbamoyl phosphate synthase 1]-N6-succinyl-L-lysine
nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-succinyl-ADP ribose
deletion of Sirt5 in mice increases the level of succinylation on carbamoyl phosphate synthase 1
-
-
?
NAD+ + [carbamoyl phosphate synthetase 1 derived glutarylated peptide]-N6-acetyl-L-lysine
nicotinamide + [carbamoyl phosphate synthetase 1 derived glutarylated peptide]-L-lysine + 2'-O-acetyl-ADP-ribose
-
-
-
?
NAD+ + [carbamoyl phosphate synthetase 1]-N6-acetyl-L-lysine
nicotinamide + [carbamoyl phosphate synthetase 1]-L-lysine + 2'-O-acetyl-ADP ribose
NAD+ + [carbamoyl phosphate synthetase 1]-N6-glutaryl-L-lysine
nicotinamide + [carbamoyl phosphate synthetase 1]-L-lysine + 2'-O-glutaryl-ADP-ribose
-
-
-
?
NAD+ + [chicken histone]-N6-acetyl-L-lysine
nicotinamide + [chicken histone]-L-lysine + 2'-O-acetyl-ADP-ribose
chemically acetylated chicken histone. Less activity toward chemically acetylated bovine serum albumin and monoacetylated histone H4 (K16 and K8). No activity is observed with monoacetylated histone K5 and K12 histone H4 peptides
-
-
?
NAD+ + [Cu/Zn superoxide dismutase]-N6-succinyl-L-lysine123
nicotinamide + [Cu/Zn superoxide dismutase]-L-lysine123 + 2'-O-succinyl-ADP-ribose
NAD+ + [cytochrome c]-N6-acetyl-L-lysine
nicotinamide + [cytochrome c]-L-lysine + 2'-O-acetyl-ADP-ribose
-
-
-
?
NAD+ + [forkhead box O3]-N6-acetyl-L-lysine
nicotinamide + [forkhead box O3]-L-lysine + 2'-O-acetyl-ADP-ribose
-
the enzyme deacetylates FOXO3 at K271 and K290
-
-
?
NAD+ + [glucose 6-phosphate dehydrogenase]-N6-succinyl-L-lysine
nicotinamide + [glucose 6-phosphate dehydrogenase]-L-lysine + 2'-O-succinyl-ADP-ribose
-
-
-
?
NAD+ + [glucose-6-phosphate dehydrogenase]-N6-acetyl-L-lysine
nicotinamide + [glucose-6-phosphate dehydrogenase]-L-lysine + 2'-O-acetyl-ADP-ribose
-
-
-
-
?
NAD+ + [glutaminase]-N6-succinyl-L-lysine
nicotinamide + [glutaminase]-L-lysine + 2'-O-succinyl-ADP-ribose
NAD+ + [glyceraldehyde-3-phosphate dehydrogenase]-N6-malonyl-L-lysine
nicotinamide + [glyceraldehyde-3-phosphate dehydrogenase]-L-lysine + 2'-O-malonyl-ADP-ribose
-
-
-
?
NAD+ + [histone H2A]-N6-succinyl-L-lysine95
nicotinamide + [histone H2A]-L-lysine95 + 2'-O-succinyl-ADP-ribose
complete desuccinylation
-
-
?
NAD+ + [histone H2A]-N6-succinyl-L-lysine9_(4-15)-A10G peptide
nicotinamide + [histone H2A]-L-lysine9_(4-15)-A10G peptide + 2'-O-succinyl-ADP-ribose
partial desuccinylation, mutant peptide substrate
-
-
?
NAD+ + [histone H2B]-N6-succinyl-L-lysine116
nicotinamide + [histone H2B]-L-lysine116 + 2'-O-succinyl-ADP-ribose
complete desuccinylation
-
-
?
NAD+ + [histone H2B]-N6-succinyl-L-lysine120
nicotinamide + [histone H2B]-L-lysine120 + 2'-O-succinyl-ADP-ribose
complete desuccinylation
-
-
?
NAD+ + [histone H2B]-N6-succinyl-L-lysine34
nicotinamide + [histone H2B]-L-lysine34 + 2'-O-succinyl-ADP-ribose
complete desuccinylation
-
-
?
NAD+ + [histone H2B]-N6-succinyl-L-lysine9
nicotinamide + [histone H2B]-L-lysine9 + 2'-O-succinyl-ADP-ribose
NAD+ + [histone H3 K9 peptide]-N6-acetyl-L-lysine
nicotinamide + [histone H3 K9 peptide]-L-lysine + 2'-O-acetyl-ADP-ribose
-
-
-
-
?
NAD+ + [histone H3 K9 peptide]-N6-succinyl-L-lysine
nicotinamide + [histone H3 K9 peptide]-L-lysine + 2'-O-succinyl-ADP-ribose
-
-
-
-
?
NAD+ + [histone H3]-N6-succinyl-L-lysine122
nicotinamide + [histone H3]-L-lysine122 + 2'-O-succinyl-ADP-ribose
complete desuccinylation
-
-
?
NAD+ + [histone H3]-N6-succinyl-L-lysine14
nicotinamide + [histone H3]-L-lysine14 + 2'-O-succinyl-ADP-ribose
partial desuccinylation, low activity
-
-
?
NAD+ + [histone H3]-N6-succinyl-L-lysine14_(9-20)-A15G peptide
nicotinamide + [histone H3]-L-lysine14_(9-20)-A15G peptide + 2'-O-succinyl-ADP-ribose
partial desuccinylation, mutant peptide substrate
-
-
?
NAD+ + [histone H3]-N6-succinyl-L-lysine56
nicotinamide + [histone H3]-L-lysine56 + 2'-O-succinyl-ADP-ribose
complete desuccinylation
-
-
?
NAD+ + [histone H3]-N6-succinyl-L-lysine79
nicotinamide + [histone H3]-L-lysine79 + 2'-O-succinyl-ADP-ribose
partial desuccinylation
-
-
?
NAD+ + [histone H3]-N6-succinyl-L-lysine9
nicotinamide + [histone H3]-L-lysine9 + 2'-O-succinyl-ADP-ribose
complete desuccinylation
-
-
?
NAD+ + [histone H4]-N6-acetyl-L-lysine16
nicotinamide + [histone H4]-L-lysine16 + 2'-O-acetyl-ADP-ribose
deacetylation, cf. EC 2.3.1.286
-
-
?
NAD+ + [histone H4]-N6-succinyl-L-lysine12
nicotinamide + [histone H4]-L-lysine12 + 2'-O-succinyl-ADP-ribose
partial desuccinylation
-
-
?
NAD+ + [histone H4]-N6-succinyl-L-lysine31
nicotinamide + [histone H4]-L-lysine31 + 2'-O-succinyl-ADP-ribose
-
-
-
?
NAD+ + [histone H4]-N6-succinyl-L-lysine31_(26-37)-P32A peptide
nicotinamide + [histone H4]-L-lysine31_(26-37)-P32A peptide + 2'-O-succinyl-ADP-ribose
partial desuccinylation, mutant peptide substrate
-
-
?
NAD+ + [histone H4]-N6-succinyl-L-lysine77
nicotinamide + [histone H4]-L-lysine77 + 2'-O-succinyl-ADP-ribose
almost complete desuccinylation
-
-
?
NAD+ + [histone H4]-N6-succinyl-L-lysine91
nicotinamide + [histone H4]-L-lysine91 + 2'-O-succinyl-ADP-ribose
complete desuccinylation
-
-
?
NAD+ + [IDH2]-N6-succinyl-L-lysine
nicotinamide + [IDH2]-L-lysine + 2'-O-succinyl-ADP-ribose
i.e. isocitrate dehydrogenase [NADP+]
-
-
?
NAD+ + [isocitrate dehydrogenase 2]-N6-acetyl-L-lysine
nicotinamide + [isocitrate dehydrogenase 2]-L-lysine + 2'-O-acetyl-ADP-ribose
-
-
-
-
?
NAD+ + [N-hydroxyarylamine O-acetyltransferase]-N6-acetyl-L-lysine
nicotinamide + [N-hydroxyarylamine O-acetyltransferase]-L-lysine + 2'-O-acetyl-ADP-ribose
NAD+ + [peptide derived from carbamoyl phosphate synthetase 1]-N6-acetyl-L-lysine
nicotinamide + [peptide derived from carbamoyl phosphate synthetase 1]-L-lysine + 2'-O-acetyl-ADP-ribose
-
-
-
?
NAD+ + [protein]-N6-acetyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose
NAD+ + [protein]-N6-malonyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-malonyl-ADP-ribose
NAD+ + [protein]-N6-succinyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
NAD+ + [PrpE protein]-N6-acetyl-L-lysine
nicotinamide + [PrpE protein]-L-lysine + 2'-O-acetyl-ADP ribose
-
-
-
-
?
NAD+ + [PrpE protein]-N6-propionyl-L-lysine
nicotinamide + [PrpE protein]-L-lysine + 2'-O-propionyl-ADP-ribose
NAD+ + [pyruvate dehydrogenase complex]-N6-succinyl-L-lysine
nicotinamide + [pyruvate dehydrogenase complex]-L-lysine + O-succinyl-ADP-ribose
NAD+ + [pyruvate kinase M2]-N6-succinyl-L-lysine311
nicotinamide + [pyruvate kinase M2]-L-lysine311 + 2'-O-succinyl-ADP-ribose
NAD+ + [RcsB protein]-N6-acetyl-L-lysine180
nicotinamide + [RcsB protein]-L-lysine180 + 2'-O-acetyl-ADP-ribose
NAD+ + [response regulator CheY]-N6-acetyl-L-lysine
nicotinamide + [response regulator CheY]-L-lysine + 2'-O-acetyl-ADP-ribose
NAD+ + [succinate dehydrogenase]-N6-succinyl-L-lysine
nicotinamide + [succinate dehydrogenase]-L-lysine + O-succinyl-ADP-ribose
NAD+ + [urate oxidase]-N6-acetyl-L-lysine
nicotinamide + [urate oxidase]-L-lysine + 2'-O-acetyl-ADP-ribose
NAD+ + FKRGVL(N6-acetyl)KEYGVKV
nicotinamide + FKRGVLKEYGVKV + 2'-O-acetyl-ADP-ribose
acetylated peptide derived from carbamoylphosphate synthetase 1 (CPS1)
-
-
?
NAD+ + FKRGVL(N6-acetyl)KEYGVKV
nicotinamide + FKRGVLKEYGVKV + 2'-O-acetyl-ADP-ribose
carbamoyl phosphate synthetase 1 Lys527 peptide
-
-
?
NAD+ + KGLGKGGA(N6-acetyl)KRHRKW
nicotinamide + KGLGKGGAKRHRKW + 2'-O-acetyl-ADP-ribose
the rate of desuccinylation is about 5fold faster than the rate of deacetylation
-
-
?
NAD+ + KGLGKGGA(N6-acetyl)KRHRKW
nicotinamide + KGLGKGGAKRHRKW + 2'-O-acetyl-ADP-ribose
-
the rate of desuccinylation is 2.3fold faster than the rate of deacetylation
-
-
?
NAD+ + KGLGKGGA(N6-butyryl)KRHRKW
nicotinamide + KGLGKGGAKRHRKW + 2'-O-butyryl-ADP-ribose
the rate of desuccinylation is about 10fold faster than the rate of debutyrylation
-
-
?
NAD+ + KGLGKGGA(N6-butyryl)KRHRKW
nicotinamide + KGLGKGGAKRHRKW + 2'-O-butyryl-ADP-ribose
-
the rate of desuccinylation is 5.8fold faster than the rate of deburyrylation
-
-
?
NAD+ + KGLGKGGA(N6-propionyl)KRHRKW
nicotinamide + KGLGKGGAKRHRKW + 2'-O-propionyl-ADP-ribose
the rate of desuccinylation is about 5fold faster than the rate of depropionylation
-
-
?
NAD+ + KGLGKGGA(N6-propionyl)KRHRKW
nicotinamide + KGLGKGGAKRHRKW + 2'-O-propionyl-ADP-ribose
-
the rate of desuccinylation is 3.8fold faster than the rate of depropionylation
-
-
?
NAD+ + KGLGKGGA(N6-succinyl)KRHRKW
nicotinamide + KGLGKGGAKRHRKW + 2'-O-succinyl-ADP-ribose
the rate of desuccinylation is about 5fold faster than the rate of deacetylation
-
-
?
NAD+ + KGLGKGGA(N6-succinyl)KRHRKW
nicotinamide + KGLGKGGAKRHRKW + 2'-O-succinyl-ADP-ribose
-
the rate of desuccinylation is 2.3fold faster than the rate of deacetylation
-
-
?
NAD+ + [acetyl-coenzyme A synthetase]-N6-acetyl-L-lysine609
nicotinamide + [acetyl-coenzyme A synthetase]-L-lysine609 + 2'-O-acetyl-ADP-ribose
-
-
-
-
?
NAD+ + [acetyl-coenzyme A synthetase]-N6-acetyl-L-lysine609
nicotinamide + [acetyl-coenzyme A synthetase]-L-lysine609 + 2'-O-acetyl-ADP-ribose
-
deacetylation by CobB activates the acetyl-coenzyme A synthetase
-
-
?
NAD+ + [ATP synthase]-N6-succinyl-L-lysine
nicotinamide + [ATP synthase]-L-lysine + 2'-O-succinyl-ADP-ribose
-
-
-
?
NAD+ + [ATP synthase]-N6-succinyl-L-lysine
nicotinamide + [ATP synthase]-L-lysine + 2'-O-succinyl-ADP-ribose
-
-
-
?
NAD+ + [carbamoyl phosphate synthase 1]-N6-acetyl-L-lysine
nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-acetyl-ADP ribose
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NAD+ + [carbamoyl phosphate synthase 1]-N6-acetyl-L-lysine
nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-acetyl-ADP ribose
SIRT5 deacetylates carbamoyl phosphate synthetase 1 (CPS1), an enzyme which is the first and rate-limiting step of urea cycle. Deacetylation of CPS1 by SIRT5 results in activation of CPS1 enzymatic activity
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NAD+ + [carbamoyl phosphate synthase 1]-N6-acetyl-L-lysine
nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-acetyl-ADP-ribose
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NAD+ + [carbamoyl phosphate synthase 1]-N6-acetyl-L-lysine
nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-acetyl-ADP-ribose
SIRT5 deacetylates carbamoyl phosphate synthetase 1 (CPS1), an enzyme which is the first and rate-limiting step of urea cycle
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NAD+ + [carbamoyl phosphate synthetase 1]-N6-acetyl-L-lysine
nicotinamide + [carbamoyl phosphate synthetase 1]-L-lysine + 2'-O-acetyl-ADP ribose
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NAD+ + [carbamoyl phosphate synthetase 1]-N6-acetyl-L-lysine
nicotinamide + [carbamoyl phosphate synthetase 1]-L-lysine + 2'-O-acetyl-ADP ribose
SIRT5 plays a pivotal role in ammonia detoxification and disposal by activating carbamoyl phosphate synthetase 1 (CPS1) an enzyme, catalyzing the initial step of the urea cycle for ammonia detoxification and disposal. SIRT5 deacetylates CPS1 and up-regulates its activity. During fasting, NAD+ in liver mitochondria increases, thereby triggering SIRT5 deacetylation of CPS1 and adaptation to the increase in amino acid catabolism. Indeed, SIRT5 KO mice fail to up-regulate CPS1 activity and show elevated blood ammonia during fasting
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NAD+ + [Cu/Zn superoxide dismutase]-N6-succinyl-L-lysine123
nicotinamide + [Cu/Zn superoxide dismutase]-L-lysine123 + 2'-O-succinyl-ADP-ribose
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NAD+ + [Cu/Zn superoxide dismutase]-N6-succinyl-L-lysine123
nicotinamide + [Cu/Zn superoxide dismutase]-L-lysine123 + 2'-O-succinyl-ADP-ribose
SIRT5 binds to, desuccinylates and activates the key antioxidant enzyme Cu/Zn superoxide dismutase (SOD1). SOD1-mediated reduction of reactive oxygen species (ROS) is increased when SIRT5 is co-expressed. Posttranslational regulation of SOD1 by means of succinylation and SIRT5-dependent desuccinylation is important for the growth of lung tumor cells
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NAD+ + [glutaminase]-N6-succinyl-L-lysine
nicotinamide + [glutaminase]-L-lysine + 2'-O-succinyl-ADP-ribose
SIRT5 desuccinylates glutaminase residue K164 to block ubiquitination of K158
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NAD+ + [glutaminase]-N6-succinyl-L-lysine
nicotinamide + [glutaminase]-L-lysine + 2'-O-succinyl-ADP-ribose
succinylation of glutaminase residue K164, no activity with K164R-GLS variant
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NAD+ + [histone H2B]-N6-succinyl-L-lysine9
nicotinamide + [histone H2B]-L-lysine9 + 2'-O-succinyl-ADP-ribose
partial desuccinylation
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NAD+ + [histone H2B]-N6-succinyl-L-lysine9
nicotinamide + [histone H2B]-L-lysine9 + 2'-O-succinyl-ADP-ribose
partial desuccinylation
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NAD+ + [N-hydroxyarylamine O-acetyltransferase]-N6-acetyl-L-lysine
nicotinamide + [N-hydroxyarylamine O-acetyltransferase]-L-lysine + 2'-O-acetyl-ADP-ribose
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NAD+ + [N-hydroxyarylamine O-acetyltransferase]-N6-acetyl-L-lysine
nicotinamide + [N-hydroxyarylamine O-acetyltransferase]-L-lysine + 2'-O-acetyl-ADP-ribose
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?
NAD+ + [protein]-N6-acetyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose
the enzyme regulates protein function in diverse and often essential cellular processes, most notably translation
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NAD+ + [protein]-N6-acetyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose
the enzyme can deacetylate acetyllysine independently whether the acetyl donor is acetyl-Coenzyme A or acetyl phosphate. Linear sequences alone are inadequate to predict CobB substrates and that structural analyses are necessary. CobB substrate acetyllyines appear to be located near the surface of the protein on a
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NAD+ + [protein]-N6-acetyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose
weak deacetylase activity
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NAD+ + [protein]-N6-malonyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-malonyl-ADP-ribose
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NAD+ + [protein]-N6-malonyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-malonyl-ADP-ribose
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?
NAD+ + [protein]-N6-succinyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
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?
NAD+ + [protein]-N6-succinyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
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NAD+ + [protein]-N6-succinyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
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NAD+ + [protein]-N6-succinyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
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?
NAD+ + [protein]-N6-succinyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
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NAD+ + [protein]-N6-succinyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
protein lysine succinylation may represent a posttranslational modification that can be reversed by Sirt5 in vivo. Lysine succinylation occurs on several mammalian proteins
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NAD+ + [protein]-N6-succinyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
strong succinylase activity
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NAD+ + [protein]-N6-succinyl-L-lysine
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
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NAD+ + [PrpE protein]-N6-propionyl-L-lysine
nicotinamide + [PrpE protein]-L-lysine + 2'-O-propionyl-ADP-ribose
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?
NAD+ + [PrpE protein]-N6-propionyl-L-lysine
nicotinamide + [PrpE protein]-L-lysine + 2'-O-propionyl-ADP-ribose
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N-Lysine propionylation controls the activity of propionyl-CoA synthetase
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NAD+ + [pyruvate dehydrogenase complex]-N6-succinyl-L-lysine
nicotinamide + [pyruvate dehydrogenase complex]-L-lysine + O-succinyl-ADP-ribose
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NAD+ + [pyruvate dehydrogenase complex]-N6-succinyl-L-lysine
nicotinamide + [pyruvate dehydrogenase complex]-L-lysine + O-succinyl-ADP-ribose
SIRT5 represses biochemical activity of, and cellular respiration through, the protein complex
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NAD+ + [pyruvate kinase M2]-N6-succinyl-L-lysine311
nicotinamide + [pyruvate kinase M2]-L-lysine311 + 2'-O-succinyl-ADP-ribose
SIRT5 desuccinylates and activates PKM2
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NAD+ + [pyruvate kinase M2]-N6-succinyl-L-lysine311
nicotinamide + [pyruvate kinase M2]-L-lysine311 + 2'-O-succinyl-ADP-ribose
SIRT5 also desuccinylates recombinant Flag-tagged PKM2 substrate, but does not but affect its malonylation and glutarylation. The K311E mutation and K311E/K498E double mutation of PKM2 both increase the succinylation level of PKM2 by about 25%, while mutations K62R/E, K135R/E, and K498R/E have no significant effect
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NAD+ + [RcsB protein]-N6-acetyl-L-lysine180
nicotinamide + [RcsB protein]-L-lysine180 + 2'-O-acetyl-ADP-ribose
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?
NAD+ + [RcsB protein]-N6-acetyl-L-lysine180
nicotinamide + [RcsB protein]-L-lysine180 + 2'-O-acetyl-ADP-ribose
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NAD+ + [RcsB protein]-N6-acetyl-L-lysine180
nicotinamide + [RcsB protein]-L-lysine180 + 2'-O-acetyl-ADP-ribose
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acetylation of the response regulator RcsB controls transcription from the small RNA promoter rprA
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NAD+ + [RcsB protein]-N6-acetyl-L-lysine180
nicotinamide + [RcsB protein]-L-lysine180 + 2'-O-acetyl-ADP-ribose
reversible Nepsilon-Lys acetylation of transcription factors is a mode of regulation of gene expression used by all cells
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NAD+ + [response regulator CheY]-N6-acetyl-L-lysine
nicotinamide + [response regulator CheY]-L-lysine + 2'-O-acetyl-ADP-ribose
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NAD+ + [response regulator CheY]-N6-acetyl-L-lysine
nicotinamide + [response regulator CheY]-L-lysine + 2'-O-acetyl-ADP-ribose
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the enzyme regulates chemotaxis of Escherichia coli by deacetylating CheY
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NAD+ + [response regulator CheY]-N6-acetyl-L-lysine
nicotinamide + [response regulator CheY]-L-lysine + 2'-O-acetyl-ADP-ribose
Escherichia coli W3110 / ATCC 27325
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NAD+ + [response regulator CheY]-N6-acetyl-L-lysine
nicotinamide + [response regulator CheY]-L-lysine + 2'-O-acetyl-ADP-ribose
Escherichia coli W3110 / ATCC 27325
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the enzyme regulates chemotaxis of Escherichia coli by deacetylating CheY
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NAD+ + [succinate dehydrogenase]-N6-succinyl-L-lysine
nicotinamide + [succinate dehydrogenase]-L-lysine + O-succinyl-ADP-ribose
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?
NAD+ + [succinate dehydrogenase]-N6-succinyl-L-lysine
nicotinamide + [succinate dehydrogenase]-L-lysine + O-succinyl-ADP-ribose
SIRT5 represses biochemical activity of, and cellular respiration through, the protein complex
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NAD+ + [urate oxidase]-N6-acetyl-L-lysine
nicotinamide + [urate oxidase]-L-lysine + 2'-O-acetyl-ADP-ribose
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?
NAD+ + [urate oxidase]-N6-acetyl-L-lysine
nicotinamide + [urate oxidase]-L-lysine + 2'-O-acetyl-ADP-ribose
SIRT5 activates urate oxidase through deacetylation in mouse liver mitochondria
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additional information
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it is proposed that YfiQ and CobB catalyze the reversible acetylation of a protein that mediates carbon-induced cpxP transcription
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additional information
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global identification of CobB substrates using an Escherichia coli proteome microarray
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additional information
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the enzyme shows dual enzymatic activities to catalyze the removal of two structurally different lysine acyl groups, acetyl and succinyl, from the modified lysine residues
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additional information
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global identification of CobB substrates using an Escherichia coli proteome microarray
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additional information
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catalytic efficiency (kcat/Km) of Sirt5 with the histone H3K9 acetyl peptide is about 500fold lower than that of Sirt1. Sirtuin 5 has only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr102 and Arg105) that bind to malonylated and succinylated substrates and define the specificity
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additional information
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no activity with Ac-Leu-Gly-(N6-acetyl)Lys-7-amido-4-methylcoumarin
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additional information
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no activity with Ac-Leu-Gly-(N6-acetyl)Lys-7-amido-4-methylcoumarin
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additional information
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Sirt5 does not deacetylate glutamate dehydrogenase or isocitrate dehydrogenase 2
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additional information
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Sirt5 does not deacetylate glutamate dehydrogenase or isocitrate dehydrogenase 2
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additional information
?
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Sirt5 catalyzes the desuccinylation of histone peptides, molecular mechanism, overview. Human Sirt5 is a ubiquitous desuccinylase that catalyzes the desuccinylation of diverse histone succinyl sites with sequence selectivity. Among the 13 identified sites, H2BK116su is the most favorable Sirt5 substrate, with H4K12su showing the lowest catalytic efficiency and no activity observed in the presence of H4K31su
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additional information
?
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Sirt5 catalyzes the desuccinylation of histone peptides, molecular mechanism, overview. Human Sirt5 is a ubiquitous desuccinylase that catalyzes the desuccinylation of diverse histone succinyl sites with sequence selectivity. Among the 13 identified sites, H2BK116su is the most favorable Sirt5 substrate, with H4K12su showing the lowest catalytic efficiency and no activity observed in the presence of H4K31su
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additional information
?
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SIRT5 catalyzes the removal of negatively charged lysine acyl modifications: succinyl, malonyl, and glutaryl groups. SIRT5 is selective only for 3-5 carbon chains acidic acyl modifications, and displays no detectable activity against either an acetyl modification, a neutral 2 carbon group, or an adipoyl, a 6-carbon acidic modification
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additional information
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SIRT5 electrostatically binds to cardiolipin and desuccinylates mitochondrial inner membrane proteins including multiple subunits of all four electron transport chain (ETC) complexes and ATP synthase. SIRT5 targets lysines at the protein-lipid interface of Complex II. Mass spectrometry identifies 14 SIRT5 target sites on the SDHA subunit of Complex II and another eight on SDHB. Molecular modeling reveals that six of the eight SIRT5 target sites on SDHB orient toward the predicted membrane interface where SDHB interacts with SDHC/SDHD
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additional information
?
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SIRT5 electrostatically binds to cardiolipin and desuccinylates mitochondrial inner membrane proteins including multiple subunits of all four electron transport chain (ETC) complexes and ATP synthase. SIRT5 targets lysines at the protein-lipid interface of Complex II. Mass spectrometry identifies 14 SIRT5 target sites on the SDHA subunit of Complex II and another eight on SDHB. Molecular modeling reveals that six of the eight SIRT5 target sites on SDHB orient toward the predicted membrane interface where SDHB interacts with SDHC/SDHD
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additional information
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essential role for the conserved main chain hydrogen bonds formed by the succinyl lysine (0), +1, and +3 sites for substrate-enzyme recognition. A proline residue at the +1 site of the histone succinylation substrate is unfavorable for Sirt5 interaction. Molecular mechanism underlying the sequence-selective desuccinylase activity of Sirt5, overview. No activity with H4K31su, and mutant substrates H3K9(4-15)-S10Psu and H3K56(51-62)-S57Psu. Usage of peptides of histone substrates
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additional information
?
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essential role for the conserved main chain hydrogen bonds formed by the succinyl lysine (0), +1, and +3 sites for substrate-enzyme recognition. A proline residue at the +1 site of the histone succinylation substrate is unfavorable for Sirt5 interaction. Molecular mechanism underlying the sequence-selective desuccinylase activity of Sirt5, overview. No activity with H4K31su, and mutant substrates H3K9(4-15)-S10Psu and H3K56(51-62)-S57Psu. Usage of peptides of histone substrates
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additional information
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synthsis of substrate peptide (2-Abz)-GVLK (succ)A [Y (3-NO2)]GV-NH2
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additional information
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synthsis of substrate peptide (2-Abz)-GVLK (succ)A [Y (3-NO2)]GV-NH2
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additional information
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Sirt5 shows negligible activity toward lysine deacetylation
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additional information
?
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SIRT5 catalyzes the removal of negatively charged lysine acyl modifications: succinyl, malonyl, and glutaryl groups. SIRT5 is selective only for 3-5 carbon chains acidic acyl modifications, and displays no detectable activity against either an acetyl modification, a neutral 2 carbon group, or an adipoyl, a 6-carbon acidic modification
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additional information
?
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SIRT5 modifies lysine succinylation, malonylation, and glutarylation
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additional information
?
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three-dimensional modeling of Complex II suggests that several SIRT5-targeted lysine residues lie at the protein-lipid interface of succinate dehydrogenase subunit B. Succinylation at these sites may disrupt Complex II subunit-subunit interactions and electron transfer. SIRT5 electrostatically binds to cardiolipin and desuccinylates mitochondrial inner membrane proteins including multiple subunits of all four electron transport chain (ETC) complexes and ATP synthase. SIRT5 targets lysines at the protein-lipid interface of Complex II
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additional information
?
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three-dimensional modeling of Complex II suggests that several SIRT5-targeted lysine residues lie at the protein-lipid interface of succinate dehydrogenase subunit B. Succinylation at these sites may disrupt Complex II subunit-subunit interactions and electron transfer. SIRT5 electrostatically binds to cardiolipin and desuccinylates mitochondrial inner membrane proteins including multiple subunits of all four electron transport chain (ETC) complexes and ATP synthase. SIRT5 targets lysines at the protein-lipid interface of Complex II
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additional information
?
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protein malonylation and succinylation lysine sites are identified by immunoprecipitation coupled lipid chromatography-tandem mass spectrometry (LC-MS/MS) methods
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additional information
?
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protein malonylation and succinylation lysine sites are identified by immunoprecipitation coupled lipid chromatography-tandem mass spectrometry (LC-MS/MS) methods
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additional information
?
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protein malonylation and succinylation lysine sites are identified by immunoprecipitation coupled lipid chromatography-tandem mass spectrometry (LC-MS/MS) methods
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