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
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2.3.1.B43
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sirtuins
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sirt3
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deacetylation
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deacetylases
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desuccinylation
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malonylation
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nad-dependent
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sirt1-7
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glutarylation
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diagnostics
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medicine
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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
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results (Engineering
Engineering on EC 2.3.1.B43 - protein-lysine desuccinylase (NAD+)
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
D101N
the decreased NAD-dependent deacetylase activity for the mutant proteins is at least partly due to reduced binding affinities for NAD+
F159A
the Km value of the mutant enzyme is twice that of wild type enzyme, whereas the kcat is 5fold less. In the F159A mutant, two water molecules occupy the position of the Phe159 ring
H80N
mutant retains about 60% of the NAD binding ability of wild type Sir2
S24A
the decreased NAD-dependent deacetylase activity for the mutant proteins is at least partly due to reduced binding affinities for NAD+
R95M
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desuccinylation decreases about 100fold, deacetylation decreases about 3fold
Y92F
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desuccinylation decreases about 42fold, deacetylation decreases about 3fold
H158Y
R105L
Y102A
the mutant enzyme catalyzes both deacetylation and desuccinylation reactions with comparable efficiencies
Y102A/R105I
the mutant enzyme favores the deacetylase reaction over the desuccinylation reaction
H158Y
additional information
H158Y
site-directed mutagenesis, catalytically inactive mutant, method, overview
R105L
mutant retains wild-type deacetylation activity and partially gains Sirt3-like nicotinamide sensitivity (IC50: 0.189 mM)
R105L
the mutant enzyme favores the deacetylase reaction over the desuccinylation reaction
H158Y
site-directed mutagenesis, like the wild-type enzyme, mutant SIRT5-H158Y overexpression significantly increases secondary LPS stimulation-induced interleukin-6 and TNF-alpha production in RAW264.7 cells
additional information
CRISPR (clustered regularly interspaced short palindromic repeats) is used to delete SIRT5 in human cell line HEK-293
additional information
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CRISPR (clustered regularly interspaced short palindromic repeats) is used to delete SIRT5 in human cell line HEK-293
additional information
knockdown of SIRT5 in induced onco-Dbl MEFs inhibits cell proliferation. Knockdown of SIRT5 also decreased the volume and number of colonies formed by the induced onco-Dbl MEFs in anchorage-independent growth assays. In breast cancer and lung cancer cell lines, SIRT5 knockdowns again inhibits proliferation and anchorage-independent growth. Expression of RNAi-resistant SIRT5 constructs rescue the proliferative defect caused by the SIRT5-targeted shRNAs
additional information
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knockdown of SIRT5 in induced onco-Dbl MEFs inhibits cell proliferation. Knockdown of SIRT5 also decreased the volume and number of colonies formed by the induced onco-Dbl MEFs in anchorage-independent growth assays. In breast cancer and lung cancer cell lines, SIRT5 knockdowns again inhibits proliferation and anchorage-independent growth. Expression of RNAi-resistant SIRT5 constructs rescue the proliferative defect caused by the SIRT5-targeted shRNAs
additional information
SIRT5 ectopic expression downregulates the expression of pancreatic and duodenal homeobox 1 (PDX1) and the inhibition of SIRT5 upregulated PDX1 expression. SIRT5 knockout using small interfering RNA targeting sirtuin 5
additional information
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SIRT5 ectopic expression downregulates the expression of pancreatic and duodenal homeobox 1 (PDX1) and the inhibition of SIRT5 upregulated PDX1 expression. SIRT5 knockout using small interfering RNA targeting sirtuin 5
additional information
generation of SIRT5 deletion mutant mice, homogenates prepared from whole SIRT5-/- liver show reduced Complex II-driven respiration. The enzymatic activities of Complex II and ATP synthase are also significantly reduced
additional information
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generation of SIRT5 deletion mutant mice, homogenates prepared from whole SIRT5-/- liver show reduced Complex II-driven respiration. The enzymatic activities of Complex II and ATP synthase are also significantly reduced
additional information
generation of SIRT5 knockout mice on the Sv129 background using the lentiviral SIRT5 shRNA plasmid sc-63027-SH
additional information
generation of SIRT5-KO mice. SIRT5-KO mice and wild-type controls undergo transverse aortic constriction (TAC) and are monitored for 16 weeks. In response to TAC, median survival is starkly decreased in SIRT5-KO mice compared with controls. No death is observed in the sham control groups for either genotype. SIRT5-KO mice have impaired systolic function 4 weeks post-TAC. These findings suggest that SIRT5-KO mice progress to cardiac dysfunction at an accelerated rate upon TAC-induced cardiac stress compared with controls, overview. SIRT5-KO mice demonstrate enhanced pathologic concentric hypertrophy in response to pressure overload, with key abnormalities in both cardiac relaxation and performance. Protein succinylation is increased in SIRT5KO hearts and abundant on enzymes in oxidative metabolism
additional information
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generation of SIRT5-KO mice. SIRT5-KO mice and wild-type controls undergo transverse aortic constriction (TAC) and are monitored for 16 weeks. In response to TAC, median survival is starkly decreased in SIRT5-KO mice compared with controls. No death is observed in the sham control groups for either genotype. SIRT5-KO mice have impaired systolic function 4 weeks post-TAC. These findings suggest that SIRT5-KO mice progress to cardiac dysfunction at an accelerated rate upon TAC-induced cardiac stress compared with controls, overview. SIRT5-KO mice demonstrate enhanced pathologic concentric hypertrophy in response to pressure overload, with key abnormalities in both cardiac relaxation and performance. Protein succinylation is increased in SIRT5KO hearts and abundant on enzymes in oxidative metabolism
additional information
hepatic SIRT5-overexpressing ob/ob mouse model (ob/ob-SIRT5 OE) is established by CRISPR/Cas9 gene editing tool. Analysis of commercially available Sirt5 conditional knock-in C57BL/6 mice. Identification, quantification, and analysis of the malonylome and succinylome in response to hepatic overexpression of SIRT5 in ob/ob mice. Hepatic overexpression of SIRT5 in ob/ob mice demalonylates proteins in the glycolysis/gluconeogenesis pathway to improve glucose metabolism, and desuccinylates proteins in the oxidative phosphorylation pathway to facilitate fatty acid metabolism
additional information
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hepatic SIRT5-overexpressing ob/ob mouse model (ob/ob-SIRT5 OE) is established by CRISPR/Cas9 gene editing tool. Analysis of commercially available Sirt5 conditional knock-in C57BL/6 mice. Identification, quantification, and analysis of the malonylome and succinylome in response to hepatic overexpression of SIRT5 in ob/ob mice. Hepatic overexpression of SIRT5 in ob/ob mice demalonylates proteins in the glycolysis/gluconeogenesis pathway to improve glucose metabolism, and desuccinylates proteins in the oxidative phosphorylation pathway to facilitate fatty acid metabolism
additional information
knockdown of SIRT5 expression in macrophages using siRNA
additional information
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hepatic SIRT5-overexpressing ob/ob mouse model (ob/ob-SIRT5 OE) is established by CRISPR/Cas9 gene editing tool. Analysis of commercially available Sirt5 conditional knock-in C57BL/6 mice. Identification, quantification, and analysis of the malonylome and succinylome in response to hepatic overexpression of SIRT5 in ob/ob mice. Hepatic overexpression of SIRT5 in ob/ob mice demalonylates proteins in the glycolysis/gluconeogenesis pathway to improve glucose metabolism, and desuccinylates proteins in the oxidative phosphorylation pathway to facilitate fatty acid metabolism
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