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Literature summary for 2.3.1.B43 extracted from

  • Du, J.; Zhou, Y.; Su, X.; Yu, J.J.; Khan, S.; Jiang, H.; Kim, J.; Woo, J.; Kim, J.H.; Choi, B.H.; He, B.; Chen, W.; Zhang, S.; Cerione, R.A.; Auwerx, J.; Hao, Q.; Lin, H.
    Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase (2011), Science, 334, 806-809.
    View publication on PubMedView publication on EuropePMC

Crystallization (Commentary)

Crystallization (Comment) Organism
crystal structure of Sirt5 in complex with a thioacetyl peptide is obtained, The corresponding acetyl peptide could not be crystallized with Sirt5 Homo sapiens

Protein Variants

Protein Variants Comment Organism
H158Y mutation significantly increases the Km for desuccinylation Homo sapiens
R105M mutation significantly increases the Km for desuccinylation Homo sapiens
Y102F mutation significantly increases the Km for desuccinylation Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0058
-
KQTAR(N6-malonyl)KSTGGWW pH 7.5, 37°C Homo sapiens
0.0061
-
KQTAR(N6-succinyl)KSTGGWW pH 7.5, 37°C Homo sapiens
0.0087
-
SGASE(N6-succinyl)KDIVHSGWW pH 7.5, 37°C Homo sapiens
0.014
-
SGASE(N6-malonyl)KDIVHSGWW pH 7.5, 37°C Homo sapiens
0.15
-
KTRSG(N6-succinyl)KVMRRWW pH 7.5, 37°C Homo sapiens
0.45
-
KTRSG(N6-malonyl)KVMRRWW pH 7.5, 37°C Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
NAD+ + [carbamoyl phosphate synthase 1]-N6-succinyl-L-lysine Mus musculus deletion of Sirt5 in mice increases the level of succinylation on carbamoyl phosphate synthase 1 nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-succinyl-ADP ribose
-
?
NAD+ + [protein]-N6-malonyl-L-lysine Homo sapiens
-
nicotinamide + [protein]-L-lysine + 2'-O-malonyl-ADP-ribose
-
?
NAD+ + [protein]-N6-succinyl-L-lysine Homo sapiens protein lysine succinylation may represent a posttranslational modification that can be reversed by Sirt5 in vivo. Lysine succinylation occurs on several mammalian proteins nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens Q9NXA8
-
-
Mus musculus Q8K2C6
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information 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 Homo sapiens ?
-
?
NAD+ + KQTAR(N6-malonyl)KSTGGWW histone H3K9 malonyl peptide Homo sapiens nicotinamide + KQTARKSTGGWW + 2'-O-malonyl-ADP-ribose
-
?
NAD+ + KQTAR(N6-succinyl)KSTGGWW histone H3K9 succinyl peptide Homo sapiens nicotinamide + KQTARKSTGGWW + 2'-O-succinyl-ADP-ribose
-
?
NAD+ + KTRSG(N6-malonyl)KVMRRWW
-
Homo sapiens nicotinamide + KTRSGKVMRRWW + 2'-O-malonyl-ADP-ribose
-
?
NAD+ + KTRSG(N6-succinyl)KVMRRWW ACS2 Lys628 peptide Homo sapiens nicotinamide + KTRSGKVMRRWW + 2'-O-succinyl-ADP-ribose
-
?
NAD+ + SGASE(N6-malonyl)KDIVHSGWW
-
Homo sapiens nicotinamide + SGASEKDIVHSGWW + 2'-O-malonyl-ADP-ribose
-
?
NAD+ + SGASE(N6-succinyl)KDIVHSGWW glutamate dehydrogenase Lys503 peptide Homo sapiens nicotinamide + SGASEKDIVHSGWW + 2'-O-succinyl-ADP-ribose
-
?
NAD+ + [carbamoyl phosphate synthase 1]-N6-succinyl-L-lysine deletion of Sirt5 in mice increases the level of succinylation on carbamoyl phosphate synthase 1 Mus musculus nicotinamide + [carbamoyl phosphate synthase 1]-L-lysine + 2'-O-succinyl-ADP ribose
-
?
NAD+ + [protein]-N6-malonyl-L-lysine
-
Homo sapiens nicotinamide + [protein]-L-lysine + 2'-O-malonyl-ADP-ribose
-
?
NAD+ + [protein]-N6-succinyl-L-lysine protein lysine succinylation may represent a posttranslational modification that can be reversed by Sirt5 in vivo. Lysine succinylation occurs on several mammalian proteins Homo sapiens nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
-
?

Synonyms

Synonyms Comment Organism
SIRT5
-
Homo sapiens
SIRT5
-
Mus musculus
sirtuin 5
-
Homo sapiens
sirtuin 5
-
Mus musculus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
assay at Homo sapiens

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.014
-
SGASE(N6-succinyl)KDIVHSGWW pH 7.5, 37°C Homo sapiens
0.025
-
KQTAR(N6-malonyl)KSTGGWW pH 7.5, 37°C Homo sapiens
0.028
-
SGASE(N6-malonyl)KDIVHSGWW pH 7.5, 37°C Homo sapiens
0.037
-
KQTAR(N6-succinyl)KSTGGWW pH 7.5, 37°C Homo sapiens
0.079
-
KTRSG(N6-succinyl)KVMRRWW pH 7.5, 37°C Homo sapiens
0.268
-
KTRSG(N6-malonyl)KVMRRWW pH 7.5, 37°C Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7.5
-
assay at Homo sapiens

General Information

General Information Comment Organism
malfunction deletion of Sirt5 in mice increases the level of succinylation on carbamoyl phosphate synthase 1 Mus musculus
physiological function protein lysine succinylation may represent a posttranslational modification that can be reversed by Sirt5 Mus musculus

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
0.52
-
KTRSG(N6-succinyl)KVMRRWW pH 7.5, 37°C Homo sapiens
0.6
-
KTRSG(N6-malonyl)KVMRRWW pH 7.5, 37°C Homo sapiens
1.6
-
SGASE(N6-succinyl)KDIVHSGWW pH 7.5, 37°C Homo sapiens
2
-
SGASE(N6-malonyl)KDIVHSGWW pH 7.5, 37°C Homo sapiens
4.3
-
KQTAR(N6-malonyl)KSTGGWW pH 7.5, 37°C Homo sapiens
6.1
-
KQTAR(N6-succinyl)KSTGGWW pH 7.5, 37°C Homo sapiens