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
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Reference
Reference on EC 2.3.1.B43 - protein-lysine desuccinylase (NAD+)
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Starai, V.J.; Celic, I.; Cole, R.N.; Boeke, J.D.; Escalante-Semerena, J.C.
Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine
Science
298
2390-2392
2002
Salmonella enterica
Ogura, M.; Nakamura, Y.; Tanaka, D.; Zhuang, X.; Fujita, Y.; Obara, A.; Hamasaki, A.; Hosokawa, M.; Inagaki, N.
Overexpression of SIRT5 confirms its involvement in deacetylation and activation of carbamoyl phosphate synthetase 1
Biochem. Biophys. Res. Commun.
393
73-78
2010
Mus musculus (Q8K2C6)
Nakagawa, T.; Lomb, D.J.; Haigis, M.C.; Guarente, L.
SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle
Cell
137
560-570
2009
Mus musculus (Q8K2C6)
Maurer, B.; Rumpf, T.; Scharfe, M.; Stolfa, D.A.; Schmitt, M.L.; He, W.; Verdin, E.; Sippl, W.; Jung, M.
Inhibitors of the NAD(+)-dependent protein desuccinylase and demalonylase Sirt5
ACS Med. Chem. Lett.
3
1050-1053
2012
Homo sapiens (Q9NXA8)
Nakagawa, T.; Guarente, L.
Urea cycle regulation by mitochondrial sirtuin, SIRT5
Aging
1
578-581
2009
Mus musculus (Q8K2C6)
Roessler, C.; Nowak, T.; Pannek, M.; Gertz, M.; Nguyen, G.T.; Scharfe, M.; Born, I.; Sippl, W.; Steegborn, C.; Schutkowski, M.
Chemical probing of the human sirtuin 5 active site reveals its substrate acyl specificity and peptide-based inhibitors
Angew. Chem. Int. Ed. Engl.
53
10728-10732
2014
Homo sapiens (Q9NXA8), Homo sapiens
Lin, Z.F.; Xu, H.B.; Wang, J.Y.; Lin, Q.; Ruan, Z.; Liu, F.B.; Jin, W.; Huang, H.H.; Chen, X.
SIRT5 desuccinylates and activates SOD1 to eliminate ROS
Biochem. Biophys. Res. Commun.
441
191-195
2013
Homo sapiens (Q9NXA8), Homo sapiens
Suenkel, B.; Fischer, F.; Steegborn, C.
Inhibition of the human deacylase Sirtuin 5 by the indole GW5074
Bioorg. Med. Chem. Lett.
23
143-146
2012
Homo sapiens (Q9NXA8), Homo sapiens
Tan, M.; Peng, C.; Anderson, K.A.; Chhoy, P.; Xie, Z.; Dai, L.; Park, J.; Chen, Y.; Huang, H.; Zhang, Y.; Ro, J.; Wagner, G.R.; Green, M.F.; Madsen, A.S.; Schmiesing, J.; Peterson, B.S.; Xu, G.; Ilkayeva, O.R.; Muehlbauer, M.J.; Braulke, T.; Mühlhausen, C.; Backos, D.S.; Olsen, C.A.; McGuire, P.J.; Pletcher, S.D.; Lombard, D.B.; Hirschey, M.D.; Zhao, Y.
Lysine glutarylation is a protein posttranslational modification regulated by SIRT5
Cell Metab.
19
605-617
2014
Homo sapiens (Q9NXA8)
Liu, B.; Che, W.; Zheng, C.; Liu, W.; Wen, J.; Fu, H.; Tang, K.; Zhang, J.; Xu, Y.
SIRT5: a safeguard against oxidative stress-induced apoptosis in cardiomyocytes
Cell. Physiol. Biochem.
32
1050-1059
2013
Rattus norvegicus (Q68FX9)
Buler, M.; Aatsinki, S.M.; Izzi, V.; Uusimaa, J.; Hakkola, J.
SIRT5 is under the control of PGC-1alpha and AMPK and is involved in regulation of mitochondrial energy metabolism
FASEB J.
28
3225-3237
2014
Mus musculus (Q8K2C6), Mus musculus
Zhang, Q.F.; Gu, J.; Gong, P.; Wang, X.D.; Tu, S.; Bi, L.J.; Yu, Z.N.; Zhang, Z.P.; Cui, Z.Q.; Wei, H.P.; Tao, S.C.; Zhang, X.E.; Deng, J.Y.
Reversibly acetylated lysine residues play important roles in the enzymatic activity of Escherichia coli N-hydroxyarylamine O-acetyltransferase
FEBS J.
280
1966-1979
2013
Escherichia coli, Escherichia coli AD494
Nakamura, Y.; Ogura, M.; Ogura, K.; Tanaka, D.; Inagaki, N.
SIRT5 deacetylates and activates urate oxidase in liver mitochondria of mice
FEBS Lett.
586
4076-4081
2012
Mus musculus (Q8K2C6), Mus musculus
Matsushita, N.; Yonashiro, R.; Ogata, Y.; Sugiura, A.; Nagashima, S.; Fukuda, T.; Inatome, R.; Yanagi, S.
Distinct regulation of mitochondrial localization and stability of two human Sirt5 isoforms
Genes Cells
16
190-202
2011
Homo sapiens (Q9NXA8), Homo sapiens
He, B.; Du, J.; Lin, H.
Thiosuccinyl peptides as Sirt5-specific inhibitors
J. Am. Chem. Soc.
134
1922-1925
2012
Homo sapiens (Q9NXA8), Homo sapiens
Hu, L.I.; Chi, B.K.; Kuhn, M.L.; Filippova, E.V.; Walker-Peddakotla, A.J.; Bäsell, K.; Becher, D.; Anderson, W.F.; Antelmann, H.; Wolfe, A.J.
Acetylation of the response regulator RcsB controls transcription from a small RNA promoter
J. Bacteriol.
195
4174-4186
2013
Escherichia coli
Chang, J.H.; Kim, H.C.; Hwang, K.Y.; Lee, J.W.; Jackson, S.P.; Bell, S.D.; Cho, Y.
Structural basis for the NAD-dependent deacetylase mechanism of Sir2
J. Biol. Chem.
277
34489-34498
2002
Archaeoglobus fulgidus (O28597)
Garrity, J.; Gardner, J.G.; Hawse, W.; Wolberger, C.; Escalante-Semerena, J.C.
N-Lysine propionylation controls the activity of propionyl-CoA synthetase
J. Biol. Chem.
282
30239-30245
2007
Salmonella enterica
Zhou, Y.; Zhang, H.; He, B.; Du, J.; Lin, H.; Cerione, R.A.; Hao, Q.
The bicyclic intermediate structure provides insights into the desuccinylation mechanism of human sirtuin 5 (SIRT5)
J. Biol. Chem.
287
28307-28314
2012
Homo sapiens (Q9NXA8), Homo sapiens
Feldman, J.L.; Baeza, J.; Denu, J.M.
Activation of the protein deacetylase SIRT6 by long-chain fatty acids and widespread deacylation by mammalian sirtuins
J. Biol. Chem.
288
31350-31356
2013
Homo sapiens (Q9NXA8)
Baeza, J.; Dowell, J.A.; Smallegan, M.J.; Fan, J.; Amador-Noguez, D.; Khan, Z.; Denu, J.M.
Stoichiometry of site-specific lysine acetylation in an entire proteome
J. Biol. Chem.
289
21326-21338
2014
Escherichia coli
Geng, Y.Q.; Li, T.T.; Liu, X.Y.; Li, Z.H.; Fu, Y.C.
SIRT1 and SIRT5 activity expression and behavioral responses to calorie restriction
J. Cell. Biochem.
112
3755-3761
2011
Rattus norvegicus (Q68FX9)
Madsen, A.S.; Olsen, C.A.
Substrates for efficient fluorometric screening employing the NAD-dependent sirtuin 5 lysine deacylase (KDAC) enzyme
J. Med. Chem.
55
5582-5590
2012
Homo sapiens (Q9NXA8), Homo sapiens
Zhao, K.; Chai, X.; Marmorstein, R.
Structure and substrate binding properties of cobB, a Sir2 homolog protein deacetylase from Escherichia coli
J. Mol. Biol.
337
731-741
2004
Escherichia coli (P75960), Escherichia coli
Schlicker, C.; Gertz, M.; Papatheodorou, P.; Kachholz, B.; Becker, C.F.; Steegborn, C.
Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5
J. Mol. Biol.
382
790-801
2008
Homo sapiens (Q9NXA8), Homo sapiens
Szczepankiewicz, B.G.; Dai, H.; Koppetsch, K.J.; Qian, D.; Jiang, F.; Mao, C.; Perni, R.B.
Synthesis of carba-NAD and the structures of its ternary complexes with SIRT3 and SIRT5
J. Org. Chem.
77
7319-7329
2012
Homo sapiens (Q9NXA8), Homo sapiens
AbouElfetouh, A.; Kuhn, M.L.; Hu, L.I.; Scholle, M.D.; Sorensen, D.J.; Sahu, A.K.; Becher, D.; Antelmann, H.; Mrksich, M.; Anderson, W.F.; Gibson, B.W.; Schilling, B.; Wolfe, A.J.
The E. coli sirtuin CobB shows no preference for enzymatic and nonenzymatic lysine acetylation substrate sites
Microbiologyopen
4
66-83
2015
Escherichia coli (P75960)
Peng, C.; Lu, Z.; Xie, Z.; Cheng, Z.; Chen, Y.; Tan, M.; Luo, H.; Zhang, Y.; He, W.; Yang, K.; Zwaans, B.M.; Tishkoff, D.; Ho, L.; Lombard, D.; He, T.C.; Dai, J.; Verdin, E.; Ye, Y.; Zhao, Y.
The first identification of lysine malonylation substrates and its regulatory enzyme
Mol. Cell. Proteomics
10
M111.012658
2011
Mus musculus (Q8K2C6)
Colak, G.; Xie, Z.; Zhu, A.Y.; Dai, L.; Lu, Z.; Zhang, Y.; Wan, X.; Chen, Y.; Cha, Y.H.; Lin, H.; Zhao, Y.; Tan, M.
Identification of lysine succinylation substrates and the succinylation regulatory enzyme CobB in Escherichia coli
Mol. Cell. Proteomics
12
3509-3520
2013
Escherichia coli
Park, J.; Chen, Y.; Tishkoff, D.X.; Peng, C.; Tan, M.; Dai, L.; Xie, Z.; Zhang, Y.; Zwaans, B.M.; Skinner, M.E.; Lombard, D.B.; Zhao, Y.
SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways
Mol. Cell.
50
919-930
2013
Mus musculus (Q8K2C6)
Li, R.; Gu, J.; Chen, Y.Y.; Xiao, C.L.; Wang, L.W.; Zhang, Z.P.; Bi, L.J.; Wei, H.P.; Wang, X.D.; Deng, J.Y.; Zhang, X.E.
CobB regulates Escherichia coli chemotaxis by deacetylating the response regulator CheY
Mol. Microbiol.
76
1162-1174
2010
Escherichia coli, Escherichia coli W3110 / ATCC 27325
Lima, B.P.; Antelmann, H.; Gronau, K.; Chi, B.K.; Becher, D.; Brinsmade, S.R.; Wolfe, A.J.
Involvement of protein acetylation in glucose-induced transcription of a stress-responsive promoter
Mol. Microbiol.
81
1190-1204
2011
Escherichia coli
Lutz, M.I.; Milenkovic, I.; Regelsberger, G.; Kovacs, G.G.
Distinct patterns of sirtuin expression during progression of Alzheimer's disease
Neuromolecular Med.
16
405-414
2014
Homo sapiens (Q9NXA8)
Thao, S.; Chen, C.S.; Zhu, H.; Escalante-Semerena, J.C.
Nepsilon-lysine acetylation of a bacterial transcription factor inhibits its DNA-binding activity
PLoS One
5
e15123
2010
Escherichia coli (P75960)
Fischer, F.; Gertz, M.; Suenkel, B.; Lakshminarasimhan, M.; Schutkowski, M.; Steegborn, C.
Sirt5 deacylation activities show differential sensitivities to nicotinamide inhibition
PLoS One
7
e45098
2012
Homo sapiens (Q9NXA8), Homo sapiens
Gertz, M.; Nguyen, G.T.; Fischer, F.; Suenkel, B.; Schlicker, C.; Fränzel, B.; Tomaschewski, J.; Aladini, F.; Becker, C.; Wolters, D.; Steegborn, C.
A molecular mechanism for direct sirtuin activation by resveratrol
PLoS One
7
e49761
2012
Homo sapiens (Q9NXA8), Homo sapiens
Ringel, A.E.; Roman, C.; Wolberger, C.
Alternate deacylating specificities of the archaeal sirtuins Sir2Af1 and Sir2Af2
Protein Sci.
23
1686-1697
2014
Escherichia coli, Archaeoglobus fulgidus (O28597), Archaeoglobus fulgidus
Pacella-Ince, L.; Zander-Fox, D.L.; Lane, M.
Mitochondrial SIRT5 is present in follicular cells and is altered by reduced ovarian reserve and advanced maternal age
Reprod. Fertil. Dev.
26
1072-1083
2014
Homo sapiens (Q9NXA8)
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
Science
334
806-809
2011
Homo sapiens (Q9NXA8), Mus musculus (Q8K2C6)
Schuetz, A.; Min, J.; Antoshenko, T.; Wang, C.L.; Allali-Hassani, A.; Dong, A.; Loppnau, P.; Vedadi, M.; Bochkarev, A.; Sternglanz, R.; Plotnikov, A.N.
Structural basis of inhibition of the human NAD+-dependent deacetylase SIRT5 by suramin
Structure
15
377-389
2007
Homo sapiens (Q9NXA8), Homo sapiens
Lu, W.; Zuo, Y.; Feng, Y.; Zhang, M.
SIRT5 facilitates cancer cell growth and drug resistance in non-small cell lung cancer
Tumour Biol.
35
10699-10705
2014
Homo sapiens (Q9NXA8), Homo sapiens
Wang, Y.; Zhu, Y.; Xing, S.; Ma, P.; Lin, D.
SIRT5 prevents cigarette smoke extract-induced apoptosis in lung epithelial cells via deacetylation of FOXO3
Cell Stress Chaperones
20
805-810
2015
Homo sapiens
Zhou, L.; Wang, F.; Sun, R.; Chen, X.; Zhang, M.; Xu, Q.; Wang, Y.; Wang, S.; Xiong, Y.; Guan, K.L.; Yang, P.; Yu, H.; Ye, D.
SIRT5 promotes IDH2 desuccinylation and G6PD deglutarylation to enhance cellular antioxidant defense
EMBO Rep.
17
811-822
2016
Mus musculus
Roessler, C.; Tueting, C.; Meleshin, M.; Steegborn, C.; Schutkowski, M.
A novel continuous assay for the deacylase sirtuin 5 and other deacetylases
J. Med. Chem.
58
7217-7223
2015
Homo sapiens (Q9NXA8)
Nishida, Y.; Rardin, M.J.; Carrico, C.; He, W.; Sahu, A.K.; Gut, P.; Najjar, R.; Fitch, M.; Hellerstein, M.; Gibson, B.W.; Verdin, E.
SIRT5 regulates both cytosolic and mitochondrial protein malonylation with glycolysis as a major target
Mol. Cell
59
321-332
2015
Mus musculus (Q8K2C6)
Yu, J.; Haldar, M.; Mallik, S.; Srivastava, D.K.
Role of the substrate specificity-defining residues of human SIRT5 in modulating the structural stability and inhibitory features of the enzyme
PLoS ONE
11
e0152467
2016
Homo sapiens (Q9NXA8), Homo sapiens
Rajabi, N.; Auth, M.; Troelsen, K.R.; Pannek, M.; Bhatt, D.P.; Fontenas, M.; Hirschey, M.D.; Steegborn, C.; Madsen, A.S.; Olsen, C.A.
Mechanism-based inhibitors of the human sirtuin 5 deacylase structure-activity relationship, biostructural, and kinetic insight
Angew. Chem. Int. Ed. Engl.
56
14836-14841
2017
Danio rerio (Q6DHI5), Danio rerio, Homo sapiens (Q9NXA8), Homo sapiens
Du, Y.; Hu, H.; Hua, C.; Du, K.; Wei, T.
Tissue distribution, subcellular localization, and enzymatic activity analysis of human SIRT5 isoforms
Biochem. Biophys. Res. Commun.
503
763-769
2018
Homo sapiens (Q9NXA8), Homo sapiens
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
Biochem. J.
476
211-223
2019
Homo sapiens (Q9NXA8), Homo sapiens
Wang, F.; Wang, K.; Xu, W.; Zhao, S.; Ye, D.; Wang, Y.; Xu, Y.; Zhou, L.; Chu, Y.; Zhang, C.; Qin, X.; Yang, P.; Yu, H.
SIRT5 desuccinylates and activates pyruvate kinase M2 to block macrophage IL-1beta production and to prevent DSS-induced colitis in mice
Cell Rep.
19
2331-2344
2017
Mus musculus (A0A1Y7VM56)
Liu, S.; Ji, S.; Yu, Z.J.; Wang, H.L.; Cheng, X.; Li, W.J.; Jing, L.; Yu, Y.; Chen, Q.; Yang, L.L.; Li, G.B.; Wu, Y.
Structure-based discovery of new selective small-molecule sirtuin 5 inhibitors
Chem. Biol. Drug Des.
91
257-268
2018
Homo sapiens (Q9NXA8), Homo sapiens
Kumar, S.; Lombard, D.B.
Functions of the sirtuin deacylase SIRT5 in normal physiology and pathobiology
Crit. Rev. Biochem. Mol. Biol.
53
311-334
2018
Mus musculus (A0A1Y7VM56), Homo sapiens (Q9NXA8)
Shuai, L.; Zhang, L.N.; Li, B.H.; Tang, C.L.; Wu, L.Y.; Li, J.; Li, J.Y.
SIRT5 regulates brown adipocyte differentiation and browning of subcutaneous white adipose tissue
Diabetes
68
1449-1461
2019
Mus musculus (A0A1Y7VM56)
Du, Y.; Hu, H.; Qu, S.; Wang, J.; Hua, C.; Zhang, J.; Wei, P.; He, X.; Hao, J.; Liu, P.; Yang, F.; Li, T.; Wei, T.
SIRT5 deacylates metabolism-related proteins and attenuates hepatic steatosis in ob/ob mice
EBioMedicine
36
347-357
2018
Mus musculus (A0A1Y7VM56), Mus musculus, Mus musculus C57BL/6 (A0A1Y7VM56)
Ma, Y.; Fei, X.
SIRT5 regulates pancreatic beta-cell proliferation and insulin secretion in type 2 diabetes
Exp. Therap. Med.
16
1417-1425
2018
Homo sapiens (Q9NXA8), Homo sapiens
Qin, K.; Han, C.; Zhang, H.; Li, T.; Li, N.; Cao, X.
NAD+ dependent deacetylase Sirtuin 5 rescues the innate inflammatory response of endotoxin tolerant macrophages by promoting acetylation of p65
J. Autoimmun.
81
120-129
2017
Mus musculus (Q8K2C6)
Zhang, Y.; Bharathi, S.S.; Rardin, M.J.; Lu, J.; Maringer, K.V.; Sims-Lucas, S.; Prochownik, E.V.; Gibson, B.W.; Goetzman, E.S.
Lysine desuccinylase SIRT5 binds to cardiolipin and regulates the electron transport chain
J. Biol. Chem.
292
10239-10249
2017
Mus musculus (A0A1Y7VM56), Mus musculus, Homo sapiens (Q9NXA8), Homo sapiens
Hershberger, K.A.; Abraham, D.M.; Martin, A.S.; Mao, L.; Liu, J.; Gu, H.; Locasale, J.W.; Hirschey, M.D.
Sirtuin 5 is required for mouse survival in response to cardiac pressure overload
J. Biol. Chem.
292
19767-19781
2017
Mus musculus (A0A1Y7VM56), Mus musculus
Yang, L.; He, Y.; Chen, Q.; Qian, S.; Wang, Z.
Design and synthesis of new 9-substituted norharmane derivatives as potential Sirt5 inhibitors
J. Heterocycl. Chem.
54
1457-1466
2017
Homo sapiens (Q9NXA8)
-
Kalbas, D.; Liebscher, S.; Nowak, T.; Meleshin, M.; Pannek, M.; Popp, C.; Alhalabi, Z.; Bordusa, F.; Sippl, W.; Steegborn, C.; Schutkowski, M.
Potent and selective inhibitors of human sirtuin 5
J. Med. Chem.
61
2460-2471
2018
Danio rerio (Q6DHI5), Homo sapiens (Q9NXA8), Homo sapiens
Kumar, S.; Lombard, D.B.
Generation and purification of catalytically active recombinant sirtuin5 (SIRT5) protein
Methods Mol. Biol.
1436
241-257
2016
Homo sapiens (Q9NXA8)
Greene, K.S.; Lukey, M.J.; Wang, X.; Blank, B.; Druso, J.E.; Lin, M.J.; Stalnecker, C.A.; Zhang, C.; Negron Abril, Y.; Erickson, J.W.; Wilson, K.F.; Lin, H.; Weiss, R.S.; Cerione, R.A.
SIRT5 stabilizes mitochondrial glutaminase and supports breast cancer tumorigenesis
Proc. Natl. Acad. Sci. USA
116
26625-26632
2019
Homo sapiens (Q9NXA8), Homo sapiens
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