BRENDA - Enzyme Database show

Role of the substrate specificity-defining residues of human SIRT5 in modulating the structural stability and inhibitory features of the enzyme

Yu, J.; Haldar, M.; Mallik, S.; Srivastava, D.K.; PLoS ONE 11, e0152467 (2016)

Data extracted from this reference:

Cloned(Commentary)
EC Number
Commentary
Organism
2.3.1.B43
expressed in Escherichia coli BL21(DE3) cells
Homo sapiens
Engineering
EC Number
Amino acid exchange
Commentary
Organism
2.3.1.B43
R105L
the mutant enzyme favores the deacetylase reaction over the desuccinylation reaction
Homo sapiens
2.3.1.B43
Y102A
the mutant enzyme catalyzes both deacetylation and desuccinylation reactions with comparable efficiencies
Homo sapiens
2.3.1.B43
Y102A/R105I
the mutant enzyme favores the deacetylase reaction over the desuccinylation reaction
Homo sapiens
Inhibitors
EC Number
Inhibitors
Commentary
Organism
Structure
2.3.1.B43
Isonicotinamide
-
Homo sapiens
2.3.1.B43
additional information
not inhibited by EX527 (i.e. 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide)
Homo sapiens
2.3.1.B43
nicotinamide
competitive inhibition
Homo sapiens
KM Value [mM]
EC Number
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
2.3.1.B43
0.069
-
NAD+
wild type enzyme, with [protein]-N6-succinyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.29
-
[protein]-N6-succinyl-L-lysine
wild type enzyme, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.321
-
NAD+
mutant enzyme Y102A, with [protein]-N6-succinyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.388
-
[protein]-N6-succinyl-L-lysine
mutant enzyme Y102A/R105I, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.609
-
NAD+
mutant enzyme R105I, with [protein]-N6-acetyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.72
-
[protein]-N6-acetyl-L-lysine
mutant enzyme Y102A, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
1.194
-
NAD+
mutant enzyme Y102A/R105I, with [protein]-N6-acetyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
1.605
-
NAD+
mutant enzyme Y102A, with [protein]-N6-acetyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
1.658
-
[protein]-N6-succinyl-L-lysine
mutant enzyme R105I, at 8.0 pH and 25°C
Homo sapiens
Natural Substrates/ Products (Substrates)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
2.3.1.B43
NAD+ + [protein]-N6-acetyl-L-lysine
Homo sapiens
weak deacetylase activity
nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose
-
-
?
2.3.1.B43
NAD+ + [protein]-N6-succinyl-L-lysine
Homo sapiens
strong succinylase activity
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
-
-
?
Organism
EC Number
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
2.3.1.B43
Homo sapiens
Q9NXA8
-
-
Purification (Commentary)
EC Number
Commentary
Organism
2.3.1.B43
HisTrap column chromatography and Hitrap column chromatography
Homo sapiens
Substrates and Products (Substrate)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2.3.1.B43
NAD+ + Ac-Suc-L-Lys-7-amido-4-methylcoumarin
-
739445
Homo sapiens
nicotinamide + ?
-
-
-
?
2.3.1.B43
NAD+ + Fluor-de-Lys
-
739445
Homo sapiens
nicotinamide + ?
-
-
-
?
2.3.1.B43
NAD+ + [protein]-N6-acetyl-L-lysine
weak deacetylase activity
739445
Homo sapiens
nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose
-
-
-
?
2.3.1.B43
NAD+ + [protein]-N6-succinyl-L-lysine
strong succinylase activity
739445
Homo sapiens
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
-
-
-
?
Temperature Stability [°C]
EC Number
Temperature Stability Minimum [°C]
Temperature Stability Maximum [°C]
Commentary
Organism
2.3.1.B43
52.9
-
melting temperature
Homo sapiens
Turnover Number [1/s]
EC Number
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
2.3.1.B43
0.000026
-
NAD+
mutant enzyme Y102A/R105I, with [protein]-N6-acetyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.000026
-
[protein]-N6-succinyl-L-lysine
mutant enzyme Y102A/R105I, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.000066
-
[protein]-N6-acetyl-L-lysine
mutant enzyme Y102A, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.000122
-
NAD+
mutant enzyme R105I, with [protein]-N6-acetyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.000274
-
NAD+
mutant enzyme Y102A, with [protein]-N6-succinyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.000274
-
[protein]-N6-succinyl-L-lysine
mutant enzyme R105I, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.04
-
NAD+
wild type enzyme, with [protein]-N6-succinyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.04
-
[protein]-N6-succinyl-L-lysine
wild type enzyme, at 8.0 pH and 25°C
Homo sapiens
Ki Value [mM]
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
2.3.1.B43
0.0175
-
nicotinamide
wild type enzyme, at pH 8.0 and 25°C
Homo sapiens
IC50 Value
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
2.3.1.B43
0.0111
-
wild type enzyme, with 0.05 mM NAD+, at 8.0 pH and 25°C
Homo sapiens
Isonicotinamide
2.3.1.B43
0.0347
-
wild type enzyme, at 8.0 pH and 25°C
Homo sapiens
Isonicotinamide
Cloned(Commentary) (protein specific)
EC Number
Commentary
Organism
2.3.1.B43
expressed in Escherichia coli BL21(DE3) cells
Homo sapiens
Engineering (protein specific)
EC Number
Amino acid exchange
Commentary
Organism
2.3.1.B43
R105L
the mutant enzyme favores the deacetylase reaction over the desuccinylation reaction
Homo sapiens
2.3.1.B43
Y102A
the mutant enzyme catalyzes both deacetylation and desuccinylation reactions with comparable efficiencies
Homo sapiens
2.3.1.B43
Y102A/R105I
the mutant enzyme favores the deacetylase reaction over the desuccinylation reaction
Homo sapiens
IC50 Value (protein specific)
EC Number
IC50 Value
IC50 Value Maximum
Commentary
Organism
Inhibitor
Structure
2.3.1.B43
0.0111
-
wild type enzyme, with 0.05 mM NAD+, at 8.0 pH and 25°C
Homo sapiens
Isonicotinamide
2.3.1.B43
0.0347
-
wild type enzyme, at 8.0 pH and 25°C
Homo sapiens
Isonicotinamide
Inhibitors (protein specific)
EC Number
Inhibitors
Commentary
Organism
Structure
2.3.1.B43
Isonicotinamide
-
Homo sapiens
2.3.1.B43
additional information
not inhibited by EX527 (i.e. 6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide)
Homo sapiens
2.3.1.B43
nicotinamide
competitive inhibition
Homo sapiens
Ki Value [mM] (protein specific)
EC Number
Ki Value [mM]
Ki Value maximum [mM]
Inhibitor
Commentary
Organism
Structure
2.3.1.B43
0.0175
-
nicotinamide
wild type enzyme, at pH 8.0 and 25°C
Homo sapiens
KM Value [mM] (protein specific)
EC Number
KM Value [mM]
KM Value Maximum [mM]
Substrate
Commentary
Organism
Structure
2.3.1.B43
0.069
-
NAD+
wild type enzyme, with [protein]-N6-succinyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.29
-
[protein]-N6-succinyl-L-lysine
wild type enzyme, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.321
-
NAD+
mutant enzyme Y102A, with [protein]-N6-succinyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.388
-
[protein]-N6-succinyl-L-lysine
mutant enzyme Y102A/R105I, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.609
-
NAD+
mutant enzyme R105I, with [protein]-N6-acetyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.72
-
[protein]-N6-acetyl-L-lysine
mutant enzyme Y102A, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
1.194
-
NAD+
mutant enzyme Y102A/R105I, with [protein]-N6-acetyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
1.605
-
NAD+
mutant enzyme Y102A, with [protein]-N6-acetyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
1.658
-
[protein]-N6-succinyl-L-lysine
mutant enzyme R105I, at 8.0 pH and 25°C
Homo sapiens
Natural Substrates/ Products (Substrates) (protein specific)
EC Number
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
2.3.1.B43
NAD+ + [protein]-N6-acetyl-L-lysine
Homo sapiens
weak deacetylase activity
nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose
-
-
?
2.3.1.B43
NAD+ + [protein]-N6-succinyl-L-lysine
Homo sapiens
strong succinylase activity
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
-
-
?
Purification (Commentary) (protein specific)
EC Number
Commentary
Organism
2.3.1.B43
HisTrap column chromatography and Hitrap column chromatography
Homo sapiens
Substrates and Products (Substrate) (protein specific)
EC Number
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
2.3.1.B43
NAD+ + Ac-Suc-L-Lys-7-amido-4-methylcoumarin
-
739445
Homo sapiens
nicotinamide + ?
-
-
-
?
2.3.1.B43
NAD+ + Fluor-de-Lys
-
739445
Homo sapiens
nicotinamide + ?
-
-
-
?
2.3.1.B43
NAD+ + [protein]-N6-acetyl-L-lysine
weak deacetylase activity
739445
Homo sapiens
nicotinamide + [protein]-L-lysine + 2'-O-acetyl-ADP-ribose
-
-
-
?
2.3.1.B43
NAD+ + [protein]-N6-succinyl-L-lysine
strong succinylase activity
739445
Homo sapiens
nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose
-
-
-
?
Temperature Stability [°C] (protein specific)
EC Number
Temperature Stability Minimum [°C]
Temperature Stability Maximum [°C]
Commentary
Organism
2.3.1.B43
52.9
-
melting temperature
Homo sapiens
Turnover Number [1/s] (protein specific)
EC Number
Turnover Number Minimum [1/s]
Turnover Number Maximum [1/s]
Substrate
Commentary
Organism
Structure
2.3.1.B43
0.000026
-
NAD+
mutant enzyme Y102A/R105I, with [protein]-N6-acetyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.000026
-
[protein]-N6-succinyl-L-lysine
mutant enzyme Y102A/R105I, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.000066
-
[protein]-N6-acetyl-L-lysine
mutant enzyme Y102A, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.000122
-
NAD+
mutant enzyme R105I, with [protein]-N6-acetyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.000274
-
NAD+
mutant enzyme Y102A, with [protein]-N6-succinyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.000274
-
[protein]-N6-succinyl-L-lysine
mutant enzyme R105I, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.04
-
NAD+
wild type enzyme, with [protein]-N6-succinyl-L-lysine as cosubstrate, at 8.0 pH and 25°C
Homo sapiens
2.3.1.B43
0.04
-
[protein]-N6-succinyl-L-lysine
wild type enzyme, at 8.0 pH and 25°C
Homo sapiens