Literature summary for 2.3.1.B43 extracted from

Hang, T.; Chen, W.; Wu, M.; Zhan, L.; Wang, C.; Jia, N.; Zhang, X.; Zang, J.
Structural insights into the molecular mechanism underlying Sirt5-catalyzed desuccinylation of histone peptides (2019), Biochem. J., 476, 211-223 .

Search for more literature for 2.3.1.B43

Cloned(Commentary)

Cloned (Comment)	Organism
gene SIRT5, recombinant expression of His-tagged enzyme in Escherichia coli strains Rosetta2(DE3) and BL21(DE3)	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant enzyme SIRT5 in complex with succinylated histones, crystals of Sirt5-H4K122su and Sirt5-H2AK95su complexes are obtained from 0.1 M sodium cacodylate, pH 5.5, and 25% w/v PEG 4000 at 22°C. Sirt5-H4K91su complex is crystallized from 0.1 M Bis-Tris, pH 5.5, and 25% w/v PEG 3350, and Sirt5-H2BK120su complex is grown in 0.2 M sodium acetate trihydrate, 0.1 M sodium cacodylate trihydrate, pH 6.5, and 30% w/v PEG 8000, X-ray diffraction structure determination and analysis at 1.70-2.30 A resolution, molecular replacement using the structures PDB ID 3RIY as a searching model	Homo sapiens

Crystallization (Comment)

Organism

purified recombinant enzyme SIRT5 in complex with succinylated histones, crystals of Sirt5-H4K122su and Sirt5-H2AK95su complexes are obtained from 0.1 M sodium cacodylate, pH 5.5, and 25% w/v PEG 4000 at 22°C. Sirt5-H4K91su complex is crystallized from 0.1 M Bis-Tris, pH 5.5, and 25% w/v PEG 3350, and Sirt5-H2BK120su complex is grown in 0.2 M sodium acetate trihydrate, 0.1 M sodium cacodylate trihydrate, pH 6.5, and 30% w/v PEG 8000, X-ray diffraction structure determination and analysis at 1.70-2.30 A resolution, molecular replacement using the structures PDB ID 3RIY as a searching model

Homo sapiens

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism
0.06051	-	[histone H3]-N6-succinyl-L-lysine122	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.06173	-	[histone H2B]-N6-succinyl-L-lysine116	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.06583	-	[histone H4]-N6-succinyl-L-lysine31_(26-37)-P32A peptide	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.07717	-	[histone H3]-N6-succinyl-L-lysine9	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.08018	-	[histone H2A]-N6-succinyl-L-lysine95	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.08268	-	[histone H4]-N6-succinyl-L-lysine77	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.08489	-	[histone H3]-N6-succinyl-L-lysine79	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.08777	-	[histone H2B]-N6-succinyl-L-lysine120	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.09551	-	[histone H3]-N6-succinyl-L-lysine14	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.09973	-	[histone H2B]-N6-succinyl-L-lysine34	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.10072	-	[histone H4]-N6-succinyl-L-lysine12	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.10178	-	[histone H4]-N6-succinyl-L-lysine91	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.10228	-	[histone H2A]-N6-succinyl-L-lysine9_(4-15)-A10G peptide	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.10442	-	[histone H3]-N6-succinyl-L-lysine14_(9-20)-A15G peptide	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.13153	-	[histone H4]-N6-succinyl-L-lysine31	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.17932	-	[histone H3]-N6-succinyl-L-lysine56	pH 7.5, 37°C, recombinant enzyme	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
mitochondrion	-	Homo sapiens	5739	-
additional information	although Sirt5 localizes mainly in the mitochondria, a slight amount of Sirt5 is detected in the nuclear fraction	Homo sapiens	-	-
nucleus	-	Homo sapiens	5634	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
additional information	Homo sapiens	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	?	-	-
NAD+ + [protein]-N6-succinyl-L-lysine	Homo sapiens	-	nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q9NXA8	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant His-tagged enzyme from Escherichia coli strain Rosetta2(DE3) by nickel affinity chromatography and gel filtration	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
additional information	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	Homo sapiens	?	-	-
additional information	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	Homo sapiens	?	-	-
NAD+ + [histone H2A]-N6-succinyl-L-lysine95	complete desuccinylation	Homo sapiens	nicotinamide + [histone H2A]-L-lysine95 + 2'-O-succinyl-ADP-ribose	-	?
NAD+ + [histone H2A]-N6-succinyl-L-lysine9_(4-15)-A10G peptide	partial desuccinylation, mutant peptide substrate	Homo sapiens	nicotinamide + [histone H2A]-L-lysine9_(4-15)-A10G peptide + 2'-O-succinyl-ADP-ribose	-	?
NAD+ + [histone H2B]-N6-succinyl-L-lysine116	complete desuccinylation	Homo sapiens	nicotinamide + [histone H2B]-L-lysine116 + 2'-O-succinyl-ADP-ribose	-	?
NAD+ + [histone H2B]-N6-succinyl-L-lysine120	complete desuccinylation	Homo sapiens	nicotinamide + [histone H2B]-L-lysine120 + 2'-O-succinyl-ADP-ribose	-	?
NAD+ + [histone H2B]-N6-succinyl-L-lysine34	complete desuccinylation	Homo sapiens	nicotinamide + [histone H2B]-L-lysine34 + 2'-O-succinyl-ADP-ribose	-	?
NAD+ + [histone H2B]-N6-succinyl-L-lysine9	partial desuccinylation	Homo sapiens	nicotinamide + [histone H2B]-L-lysine9 + 2'-O-succinyl-ADP-ribose	-	?
NAD+ + [histone H3]-N6-succinyl-L-lysine122	complete desuccinylation	Homo sapiens	nicotinamide + [histone H3]-L-lysine122 + 2'-O-succinyl-ADP-ribose	-	?
NAD+ + [histone H3]-N6-succinyl-L-lysine14	partial desuccinylation, low activity	Homo sapiens	nicotinamide + [histone H3]-L-lysine14 + 2'-O-succinyl-ADP-ribose	-	?
NAD+ + [histone H3]-N6-succinyl-L-lysine14_(9-20)-A15G peptide	partial desuccinylation, mutant peptide substrate	Homo sapiens	nicotinamide + [histone H3]-L-lysine14_(9-20)-A15G peptide + 2'-O-succinyl-ADP-ribose	-	?
NAD+ + [histone H3]-N6-succinyl-L-lysine56	complete desuccinylation	Homo sapiens	nicotinamide + [histone H3]-L-lysine56 + 2'-O-succinyl-ADP-ribose	-	?
NAD+ + [histone H3]-N6-succinyl-L-lysine79	partial desuccinylation	Homo sapiens	nicotinamide + [histone H3]-L-lysine79 + 2'-O-succinyl-ADP-ribose	-	?
NAD+ + [histone H3]-N6-succinyl-L-lysine9	complete desuccinylation	Homo sapiens	nicotinamide + [histone H3]-L-lysine9 + 2'-O-succinyl-ADP-ribose	-	?
NAD+ + [histone H4]-N6-succinyl-L-lysine12	partial desuccinylation	Homo sapiens	nicotinamide + [histone H4]-L-lysine12 + 2'-O-succinyl-ADP-ribose	-	?
NAD+ + [histone H4]-N6-succinyl-L-lysine31	-	Homo sapiens	nicotinamide + [histone H4]-L-lysine31 + 2'-O-succinyl-ADP-ribose	-	?
NAD+ + [histone H4]-N6-succinyl-L-lysine31_(26-37)-P32A peptide	partial desuccinylation, mutant peptide substrate	Homo sapiens	nicotinamide + [histone H4]-L-lysine31_(26-37)-P32A peptide + 2'-O-succinyl-ADP-ribose	-	?
NAD+ + [histone H4]-N6-succinyl-L-lysine77	almost complete desuccinylation	Homo sapiens	nicotinamide + [histone H4]-L-lysine77 + 2'-O-succinyl-ADP-ribose	-	?
NAD+ + [histone H4]-N6-succinyl-L-lysine91	complete desuccinylation	Homo sapiens	nicotinamide + [histone H4]-L-lysine91 + 2'-O-succinyl-ADP-ribose	-	?
NAD+ + [protein]-N6-succinyl-L-lysine	-	Homo sapiens	nicotinamide + [protein]-L-lysine + 2'-O-succinyl-ADP-ribose	-	?

Synonyms

Synonyms	Comment	Organism
histone desuccinylase	-	Homo sapiens
SIRT5	-	Homo sapiens

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
0.178	-	[histone H3]-N6-succinyl-L-lysine122	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.186	-	[histone H3]-N6-succinyl-L-lysine14_(9-20)-A15G peptide	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.189	-	[histone H4]-N6-succinyl-L-lysine31_(26-37)-P32A peptide	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.199	-	[histone H2A]-N6-succinyl-L-lysine9_(4-15)-A10G peptide	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.2	-	[histone H3]-N6-succinyl-L-lysine14	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.202	-	[histone H4]-N6-succinyl-L-lysine12	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.208	-	[histone H4]-N6-succinyl-L-lysine77	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.213	-	[histone H3]-N6-succinyl-L-lysine79	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.219	-	[histone H2A]-N6-succinyl-L-lysine95	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.224	-	[histone H4]-N6-succinyl-L-lysine31	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.279	-	[histone H2B]-N6-succinyl-L-lysine120	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.294	-	[histone H4]-N6-succinyl-L-lysine91	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.297	-	[histone H2B]-N6-succinyl-L-lysine116	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.314	-	[histone H2B]-N6-succinyl-L-lysine34	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.336	-	[histone H3]-N6-succinyl-L-lysine9	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
0.512	-	[histone H3]-N6-succinyl-L-lysine56	pH 7.5, 37°C, recombinant enzyme	Homo sapiens

pH Optimum

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

Cofactor

Cofactor	Comment	Organism	Structure
NAD+	-	Homo sapiens

General Information

General Information	Comment	Organism
additional information	molecular mechanism underlying the sequence-selective desuccinylase activity of Sirt5, 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	Homo sapiens
physiological function	human sirtuin 5 (Sirt5) catalyzes the sequence-selective desuccinylation of numerous histone succinyl sites. Compared with Sirt1, 2, 3, and 6, enzyme Sirt5 exhibits relatively weak deacetylation activity but can more efficiently remove negatively charged modifications, such as malonylation, glutarylation, and especially succinylation, from lysine residues. Sirt5 is considered a desuccinylase	Homo sapiens

kcat/KM [mM/s]

kcat/KM Value [1/mMs^-1]	kcat/KM Value Maximum [1/mMs^-1]	Substrate	Comment	Organism
1.7	-	[histone H4]-N6-succinyl-L-lysine31	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
1.78	-	[histone H3]-N6-succinyl-L-lysine14_(9-20)-A15G peptide	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
1.95	-	[histone H2A]-N6-succinyl-L-lysine9_(4-15)-A10G peptide	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
2.01	-	[histone H4]-N6-succinyl-L-lysine12	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
2.09	-	[histone H3]-N6-succinyl-L-lysine14	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
2.51	-	[histone H3]-N6-succinyl-L-lysine79	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
2.52	-	[histone H4]-N6-succinyl-L-lysine77	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
2.73	-	[histone H2A]-N6-succinyl-L-lysine95	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
2.86	-	[histone H3]-N6-succinyl-L-lysine56	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
2.87	-	[histone H4]-N6-succinyl-L-lysine31_(26-37)-P32A peptide	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
2.89	-	[histone H4]-N6-succinyl-L-lysine91	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
2.94	-	[histone H3]-N6-succinyl-L-lysine122	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
3.15	-	[histone H2B]-N6-succinyl-L-lysine34	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
3.18	-	[histone H2B]-N6-succinyl-L-lysine120	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
4.35	-	[histone H3]-N6-succinyl-L-lysine9	pH 7.5, 37°C, recombinant enzyme	Homo sapiens
4.81	-	[histone H2B]-N6-succinyl-L-lysine116	pH 7.5, 37°C, recombinant enzyme	Homo sapiens