1932

Abstract

Sirtuins are NAD+-dependent enzymes universally present in all organisms, where they play central roles in regulating numerous biological processes. Although early studies showed that sirtuins deacetylated lysines in a reaction that consumes NAD+, more recent studies have revealed that these enzymes can remove a variety of acyl-lysine modifications. The specificities for varied acyl modifications may thus underlie the distinct roles of the different sirtuins within a given organism. This review summarizes the structure, chemistry, and substrate specificity of sirtuins with a focus on how different sirtuins recognize distinct substrates and thus carry out specific functions.

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2016-06-02
2024-06-25
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Literature Cited

  1. Frye RA. 1.  2000. Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins. Biochem. Biophys. Res. Commun. 273:793–98 [Google Scholar]
  2. Bosch-Presegue L, Vaquero A. 2.  2015. Sirtuin-dependent epigenetic regulation in the maintenance of genome integrity. FEBS J 282:1745–67 [Google Scholar]
  3. Masri S, Sassone-Corsi P. 3.  2014. Sirtuins and the circadian clock: bridging chromatin and metabolism. Sci. Signal. 7:re6 [Google Scholar]
  4. Choi JE, Mostoslavsky R. 4.  2014. Sirtuins, metabolism, and DNA repair. Curr. Opin. Genet. Dev. 26:24–32 [Google Scholar]
  5. Ng F, Tang BL. 5.  2013. Sirtuins’ modulation of autophagy. J. Cell. Physiol. 228:2262–70 [Google Scholar]
  6. Houtkooper RH, Pirinen E, Auwerx J. 6.  2012. Sirtuins as regulators of metabolism and healthspan. Nat. Rev. Mol. Cell Biol. 13:225–38 [Google Scholar]
  7. Guarente L. 7.  2011. Sirtuins, aging, and metabolism. Cold Spring Harb. Symp. Quant. Biol. 76:81–90 [Google Scholar]
  8. Haigis MC, Sinclair DA. 8.  2010. Mammalian sirtuins: biological insights and disease relevance. Annu. Rev. Pathol. Mech. Dis. 5:253–95 [Google Scholar]
  9. Imai S, Armstrong CM, Kaeberlein M, Guarente L. 9.  2000. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature 403:795–800 [Google Scholar]
  10. Tanner KG, Landry J, Sternglanz R, Denu JM. 10.  2000. Silent information regulator 2 family of NAD-dependent histone/protein deacetylases generates a unique product, 1-O-acetyl-ADP-ribose. PNAS 97:14178–82 [Google Scholar]
  11. Landry J, Sutton A, Tafrov ST, Heller RC, Stebbins J. 11.  et al. 2000. The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases. PNAS 97:5807–11 [Google Scholar]
  12. Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR. 12.  et al. 2004. Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 23:2369–80 [Google Scholar]
  13. Luo J, Nikolaev AY, Imai S-I, Chen D, Su F. 13.  et al. 2001. Negative control of p53 by Sir2α promotes cell survival under stress. Cell 107:137–48 [Google Scholar]
  14. Vaziri H, Dessain SK, Eaton EN, Imai S-I, Frye RA. 14.  et al. 2001. hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase. Cell 107:149–59 [Google Scholar]
  15. Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P. 15.  2005. Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1. Nature 434:113–18 [Google Scholar]
  16. Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL. 16.  et al. 2004. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 303:2011–15 [Google Scholar]
  17. Hu J, Jing H, Lin H. 17.  2014. Sirtuin inhibitors as anticancer agents. Future Med. Chem. 6:945–66 [Google Scholar]
  18. Chen Y, Sprung R, Tang Y, Ball H, Sangras B. 18.  et al. 2007. Lysine propionylation and butyrylation are novel post-translational modifications in histones. Mol. Cell. Proteom. 6:812–19 [Google Scholar]
  19. Metoyer CF, Pruitt K. 19.  2008. The role of sirtuin proteins in obesity. Pathophysiology 15:103–8 [Google Scholar]
  20. Rajendrasozhan S, Yang SR, Kinnula VL, Rahman I. 20.  2008. SIRT1, an antiinflammatory and antiaging protein, is decreased in lungs of patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 177:861–70 [Google Scholar]
  21. Jiang H, Khan S, Wang Y, Charron G, He B. 21.  et al. 2013. SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine. Nature 496:110–13 [Google Scholar]
  22. Eskandarian HA, Impens F, Nahori MA, Soubigou G, Coppee JY. 22.  et al. 2013. A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection. Science 341:1238858 [Google Scholar]
  23. Pinzone MR, Cacopardo B, Condorelli F, Di Rosa M, Nunnari G. 23.  2013. Sirtuin-1 and HIV-1: an overview. Curr. Drug Targets 14:648–52 [Google Scholar]
  24. Chakraborty C, Doss CG. 24.  2013. Sirtuins family—recent development as a drug target for aging, metabolism, and age related diseases. Curr. Drug Targets 14:666–75 [Google Scholar]
  25. Brachmann CB, Sherman JM, Devine SE, Cameron EE, Pillus L, Boeke JD. 25.  1995. The SIR2 gene family, conserved from bacteria to humans, functions in silencing, cell cycle progression, and chromosome stability. Genes Dev 9:2888–902 [Google Scholar]
  26. Derbyshire MK, Weinstock KG, Strathern JN. 26.  1996. HST1, a new member of the SIR2 family of genes. Yeast 12:631–40 [Google Scholar]
  27. Du J, Zhou Y, Su X, Yu J, Khan S. 27.  et al. 2011. Sirt5 is an NAD-dependent protein lysine demalonylase and desuccinylase. Science 334:806–9 [Google Scholar]
  28. Zhu AY, Zhou Y, Khan S, Deitsch KW, Hao Q, Lin H. 28.  2012. Plasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fatty acyl lysine. ACS Chem. Biol. 7:155–59 [Google Scholar]
  29. Feldman JL, Baeza J, Denu JM. 29.  2013. Activation of the protein deacetylase SIRT6 by long-chain fatty acids and widespread deacylation by mammalian sirtuins. J. Biol. Chem. 288:31350–56 [Google Scholar]
  30. He B, Hu J, Zhang X, Lin H. 30.  2014. Thiomyristoyl peptides as cell-permeable Sirt6 inhibitors. Org. Biomol. Chem. 12:7498–502 [Google Scholar]
  31. Peng C, Lu Z, Xie Z, Cheng Z, Chen Y. 31.  et al. 2011. The first identification of lysine malonylation substrates and its regulatory enzyme. Mol. Cell. Proteom. 10:12M111.012658 [Google Scholar]
  32. Tan M, Peng C, Anderson KA, Chhoy P, Xie Z. 32.  et al. 2014. Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab. 19:605–17 [Google Scholar]
  33. Tan M, Luo H, Lee S, Jin F, Yang Jeong S. 33.  et al. 2011. Identification of 67 histone marks and histone lysine crotonylation as a new type of histone modification. Cell 146:1016–28 [Google Scholar]
  34. Zhang Z, Tan M, Xie Z, Dai L, Chen Y, Zhao Y. 34.  2011. Identification of lysine succinylation as a new post-translational modification. Nat. Chem. Biol. 7:58–63 [Google Scholar]
  35. Park J, Chen Y, Tishkoff DX, Peng C, Tan M. 35.  et al. 2013. SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways. Mol. Cell 50:919–30 [Google Scholar]
  36. Colak G, Xie Z, Zhu AY, Dai L, Lu Z. 36.  et al. 2013. Identification of lysine succinylation substrates and the succinylation regulatory enzyme CobB in Escherichia coli. Mol. Cell. Proteom. 12:3509–20 [Google Scholar]
  37. Rardin MJ, He W, Nishida Y, Newman JC, Carrico C. 37.  et al. 2013. SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks. Cell Metab. 18:920–33 [Google Scholar]
  38. Sauve AA, Wolberger C, Schramm VL, Boeke JD. 38.  2006. The biochemistry of sirtuins. Annu. Rev. Biochem. 75:435–65 [Google Scholar]
  39. Yuan H, Marmorstein R. 39.  2012. Structural basis for sirtuin activity and inhibition. J. Biol. Chem. 287:42428–35 [Google Scholar]
  40. Marmorstein R. 40.  2001. Structure of histone deacetylases: insights into substrate recognition and catalysis. Structure 9:1127–33 [Google Scholar]
  41. Shore D, Squire M, Nasmyth KA. 41.  1984. Characterization of two genes required for the position-effect control of yeast mating-type genes. EMBO J 3:2817–23 [Google Scholar]
  42. Tsang AW, Escalante-Semerena JC. 42.  1998. CobB, a new member of the SIR2 family of eucaryotic regulatory proteins, is required to compensate for the lack of nicotinate mononucleotide:5,6-dimethylbenzimidazole phosphoribosyltransferase activity in cobT mutants during cobalamin biosynthesis in Salmonella typhimurium LT2. J. Biol. Chem. 273:31788–94 [Google Scholar]
  43. Frye RA. 43.  1999. Characterization of five human cDNAs with homology to the yeast Sir2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity. Biochem. Biophys. Res. Commun. 260:273–79 [Google Scholar]
  44. Tanny JC, Dowd GJ, Huang J, Hilz H, Moazed D. 44.  1999. An enzymatic activity in the yeast Sir2 protein that is essential for gene silencing. Cell 99:735–45 [Google Scholar]
  45. Sauve AA, Celic I, Avalos J, Deng H, Boeke JD, Schramm VL. 45.  2001. Chemistry of gene silencing: the mechanism of NAD+-dependent deacetylation reactions. Biochemistry 40:15456–63 [Google Scholar]
  46. Haigis MC, Mostoslavsky R, Haigis KM, Fahie K, Christodoulou DC. 46.  et al. 2006. SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic β cells. Cell 126:941–54 [Google Scholar]
  47. Mao Z, Hine C, Tian X, Van Meter M, Au M. 47.  et al. 2011. SIRT6 promotes DNA repair under stress by activating PARP1. Science 332:1443–46 [Google Scholar]
  48. Liszt G, Ford E, Kurtev M, Guarente L. 48.  2005. Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase. J. Biol. Chem. 280:21313–20 [Google Scholar]
  49. Michishita E, Park JY, Burneskis JM, Barrett JC, Horikawa I. 49.  2005. Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. Mol. Biol. Cell 16:4623–35 [Google Scholar]
  50. Kowieski TM, Lee S, Denu JM. 50.  2008. Acetylation-dependent ADP-ribosylation by Trypanosoma brucei Sir2. J. Biol. Chem. 283:5317–26 [Google Scholar]
  51. Du J, Jiang H, Lin H. 51.  2009. Investigating the ADP-ribosyltransferase activity of sirtuins with NAD analogs and 32P-NAD. Biochemistry 48:2878–90 [Google Scholar]
  52. Lin H, Su X, He B. 52.  2012. Protein lysine acylation and cysteine succination by intermediates of energy metabolism. ACS Chem. Biol. 7:947–60 [Google Scholar]
  53. Newman JC, He W, Verdin E. 53.  2012. Mitochondrial protein acylation and intermediary metabolism: regulation by sirtuins and implications for metabolic disease. J. Biol. Chem. 287:42436–43 [Google Scholar]
  54. Smith BC, Denu JM. 54.  2006. Sir2 protein deacetylases: Evidence for chemical intermediates and functions of a conserved histidine. Biochemistry 45:272–82 [Google Scholar]
  55. Garrity J, Gardner JG, Hawse W, Wolberger C, Escalante-Semerena JC. 55.  2007. N-lysine propionylation controls the activity of propionyl-CoA synthetase. J. Biol. Chem. 282:30239–45 [Google Scholar]
  56. Xie Z, Dai J, Dai L, Tan M, Cheng Z. 56.  et al. 2012. Lysine succinylation and lysine malonylation in histones. Mol. Cell. Proteom. 11:100–7 [Google Scholar]
  57. Sauve AA, Schramm VL. 57.  2003. Sir2 regulation by nicotinamide results from switching between base exchange and deacetylation chemistry. Biochemistry 42:9249–56 [Google Scholar]
  58. Jackson MD, Denu JM. 58.  2002. Structural identification of 2′- and 3′-O-acetyl-ADP-ribose as novel metabolites derived from the Sir2 family of β-NAD+-dependent histone/protein deacetylases. J. Biol. Chem. 277:18535–44 [Google Scholar]
  59. Jackson MD, Schmidt MT, Oppenheimer NJ, Denu JM. 59.  2003. Mechanism of nicotinamide inhibition and transglycosidation by Sir2 histone/protein deacetylases. J. Biol. Chem. 278:50985–98 [Google Scholar]
  60. Smith BC, Denu JM. 60.  2007. Mechanism-based inhibition of Sir2 deacetylases by thioacetyl-lysine peptide. Biochemistry 46:14478–86 [Google Scholar]
  61. Hawse WF, Hoff KG, Fatkins DG, Daines A, Zubkova OV. 61.  et al. 2008. Structural insights into intermediate steps in the Sir2 deacetylation reaction. Structure 16:1368–77 [Google Scholar]
  62. Hoff KG, Avalos JL, Sens K, Wolberger C. 62.  2006. Insights into the sirtuin mechanism from ternary complexes containing NAD+ and acetylated peptide. Structure 14:1231–40 [Google Scholar]
  63. Zhao K, Chai X, Marmorstein R. 63.  2003. Structure of the yeast Hst2 protein deacetylase in ternary complex with 2′-O-acetyl ADP ribose and histone peptide. Structure 11:1403–11 [Google Scholar]
  64. Bedalov A, Gatbonton T, Irvine WP, Gottschling DE, Simon JA. 64.  2001. Identification of a small molecule inhibitor of Sir2p. PNAS 98:15113–18 [Google Scholar]
  65. French JB, Cen Y, Sauve AA. 65.  2008. Plasmodium falciparum Sir2 is an NAD+-dependent deacetylase and an acetyllysine-dependent and acetyllysine-independent NAD+ glycohydrolase. Biochemistry 47:10227–39 [Google Scholar]
  66. Jiang T, Zhou X, Taghizadeh K, Dong M, Dedon PC. 66.  2007. N-formylation of lysine in histone proteins as a secondary modification arising from oxidative DNA damage. PNAS 104:60–65 [Google Scholar]
  67. Cen Y, Sauve AA. 67.  2010. Transition state of ADP-ribosylation of acetyllysine catalyzed by Archaeoglobus fulgidus Sir2 determined by kinetic isotope effects and computational approaches. J. Am. Chem. Soc. 132:12286–98 [Google Scholar]
  68. Sanders BD, Jackson B, Marmorstein R. 68.  2010. Structural basis for sirtuin function: what we know and what we don't. Biochim. Biophys. Acta 1804:1604–16 [Google Scholar]
  69. Rossmann MG, Argos P. 69.  1978. The taxonomy of binding sites in proteins. Mol. Cell. Biochem. 21:161–82 [Google Scholar]
  70. Avalos JL, Celic I, Muhammad S, Cosgrove MS, Boeke JD, Wolberger C. 70.  2002. Structure of a Sir2 enzyme bound to an acetylated p53 peptide. Mol. Cell 10:523–35 [Google Scholar]
  71. Min J, Landry J, Sternglanz R, Xu R-M. 71.  2001. Crystal structure of a SIR2 homolog-NAD complex. Cell 105:269–79 [Google Scholar]
  72. Bheda P, Wang JT, Escalante-Semerena JC, Wolberger C. 72.  2011. Structure of Sir2Tm bound to a propionylated peptide. Protein Sci 20:131–39 [Google Scholar]
  73. Cosgrove MS, Bever K, Avalos JL, Muhammad S, Zhang X, Wolberger C. 73.  2006. The structural basis of sirtuin substrate affinity. Biochemistry 45:7511–21 [Google Scholar]
  74. Avalos J, Boeke JD, Wolberger C. 74.  2004. Structural basis for the mechanism and regulation of Sir2 enzymes. Mol. Cell 13:639–48 [Google Scholar]
  75. Fulco M, Schiltz RL, Iezzi S, King MT, Zhao P. 75.  et al. 2003. Sir2 regulates skeletal muscle differentiation as a potential sensor of the redox state. Mol. Cell 12:51–62 [Google Scholar]
  76. Zhao K, Chai X, Marmorstein R. 76.  2004. Structure and substrate binding properties of cobB, a Sir2 homolog protein deacetylase from Escherichia coli. J. Mol. Biol. 337:731–41 [Google Scholar]
  77. Schuetz A, Min J, Antoshenko T, Wang C-L, Allali-Hassani A. 77.  et al. 2007. Structural basis of inhibition of the human NAD+-dependent deacetylase SIRT5 by suramin. Structure 15:377–89 [Google Scholar]
  78. Borra MT, Langer MR, Slama JT, Denu JM. 78.  2004. Substrate specificity and kinetic mechanism of the Sir2 family of NAD+-dependent histone/protein deacetylases. Biochemistry 43:9877–87 [Google Scholar]
  79. Zhao K, Harshaw R, Chai X, Marmorstein R. 79.  2004. Structural basis for nicotinamide cleavage and ADP-ribose transfer by NAD+-dependent Sir2 histone/protein deacetylases. PNAS USA 101:8563–68 [Google Scholar]
  80. Zhou Y, Zhang H, He B, Du J, Lin H. 80.  et al. 2012. The bicyclic intermediate structure provides insights into the desuccinylation mechanism of human sirtuin 5 (SIRT5). J. Biol. Chem. 287:28307–14 [Google Scholar]
  81. Bell SD, Botting CH, Wardleworth BN, Jackson SP, White MF. 81.  2002. The interaction of Alba, a conserved archaeal chromatin protein, with Sir2 and its regulation by acetylation. Science 296:148–51 [Google Scholar]
  82. Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Cohen H. 82.  et al. 2002. Manipulation of a nuclear NAD+ salvage pathway delays aging without altering steady-state NAD+ levels. J. Biol. Chem. 277:18881–90 [Google Scholar]
  83. Schmidt MT, Smith BC, Jackson MD, Denu JM. 83.  2004. Coenzyme specificity of Sir2 protein deacetylases: implications for physiological regulation. J. Biol. Chem. 279:40122–29 [Google Scholar]
  84. Denu JM. 84.  2003. Linking chromatin function with metabolic networks: Sir2 family of NAD+-dependent deacetylases. Trends Biochem. Sci. 28:41–48 [Google Scholar]
  85. Avalos JL, Bever KM, Wolberger C. 85.  2005. Mechanism of sirtuin inhibition by nicotinamide: altering the NAD+ cosubstrate specificity of a Sir2 enzyme. Mol. Cell 17:855–68 [Google Scholar]
  86. Sauve AA, Moir RD, Schramm VL, Willis IM. 86.  2005. Chemical activation of Sir2-dependent silencing by relief of nicotinamide inhibition. Mol. Cell 17:595–601 [Google Scholar]
  87. Grunstein M. 87.  1997. Histone acetylation in chromatin structure and transcription. Nature 389:349–52 [Google Scholar]
  88. Starai VJ, Celic I, Cole RN, Boeke JD, Escalante-Semerena JC. 88.  2002. Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine. Science 298:2390–92 [Google Scholar]
  89. Smith BC, Denu JM. 89.  2007. Acetyl-lysine analog peptides as mechanistic probes of protein deacetylases. J. Biol. Chem. 282:37256–65 [Google Scholar]
  90. Zhang K, Chen Y, Zhang Z, Zhao Y. 90.  2008. Identification and verification of lysine propionylation and butyrylation in yeast core histones using PTMap software. J. Proteome Res. 8:900–6 [Google Scholar]
  91. Cheng Z, Tang Y, Chen Y, Kim S, Liu H. 91.  et al. 2009. Molecular characterization of propionyllysines in non-histone proteins. Mol. Cell. Proteom. 8:45–52 [Google Scholar]
  92. Liu B, Lin Y, Darwanto A, Song X, Xu G, Zhang K. 92.  2009. Identification and characterization of propionylation at histone H3 lysine 23 in mammalian cells. J. Biol. Chem. 284:32288–95 [Google Scholar]
  93. Schlicker C, Gertz M, Papatheodorou P, Kachholz B, Becker CFW, Steegborn C. 93.  2008. Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. J. Mol. Biol. 382:790–801 [Google Scholar]
  94. Nakagawa T, Lomb DJ, Haigis MC, Guarente L. 94.  2009. SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. Cell 137:560–70 [Google Scholar]
  95. Nishida Y, Rardin MJ, Carrico C, He W, Sahu AK. 95.  et al. 2015. SIRT5 regulates both cytosolic and mitochondrial protein malonylation with glycolysis as a major target. Mol. Cell 59:321–32 [Google Scholar]
  96. Ringel AE, Roman C, Wolberger C. 96.  2014. Alternate deacylating specificities of the archaeal sirtuins Sir2Af1 and Sir2Af2. Protein Sci 23:1686–97 [Google Scholar]
  97. Michishita E, McCord RA, Berber E, Kioi M, Padilla-Nash H. 97.  et al. 2008. SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature 452:492–96 [Google Scholar]
  98. Michishita E, McCord RA, Boxer LD, Barber MF, Hong T. 98.  et al. 2009. Cell cycle–dependent deacetylation of telomeric histone H3 lysine K56 by human SIRT6. Cell Cycle 8:2664–66 [Google Scholar]
  99. Yang B, Zwaans BMM, Eckersdorff M, Lombard DB. 99.  2009. The sirtuin SIRT6 deacetylates H3 K56Ac in vivo to promote genomic stability. Cell Cycle 8:2662–63 [Google Scholar]
  100. Kaidi A, Weinert BT, Choudhary C, Jackson SP. 100.  2010. Human SIRT6 promotes DNA end resection through CtIP deacetylation. Science 329:1348–53 [Google Scholar]
  101. Schwer B, Schumacher B, Lombard DB, Xiao C, Kurtev MV. 101.  et al. 2010. Neural sirtuin 6 (Sirt6) ablation attenuates somatic growth and causes obesity. PNAS 107:21790–94 [Google Scholar]
  102. Wajant H, Pfizenmaier K, Scheurich P. 102.  2003. Tumor necrosis factor signaling. Cell Death. Differ. 10:45–65 [Google Scholar]
  103. Stevenson FT, Bursten SL, Locksley RM, Lovett DH. 103.  1992. Myristyl acylation of the tumor necrosis factor α precursor on specific lysine residues. J. Exp. Med. 176:1053–62 [Google Scholar]
  104. Van Gool F, Galli M, Gueydan C, Kruys V, Prevot P-P. 104.  et al. 2009. Intracellular NAD levels regulate tumor necrosis factor protein synthesis in a sirtuin-dependent manner. Nat. Med. 15:206–10 [Google Scholar]
  105. Teng Y-B, Jing H, Aramsangtienchai P, He B, Khan S. 105.  et al. 2015. Efficient demyristoylase activity of SIRT2 revealed by kinetic and structural studies. Sci. Rep. 5:8529 [Google Scholar]
  106. Feldman JL, Dittenhafer-Reed KE, Kudo N, Thelen JN, Ito A. 106.  et al. 2015. Kinetic and structural basis for acyl-group selectivity and NAD+ dependence in sirtuin-catalyzed deacylation. Biochemistry 54:3037–50 [Google Scholar]
  107. Mathias RA, Greco TM, Oberstein A, Budayeva HG, Chakrabarti R. 107.  et al. 2014. Sirtuin 4 is a lipoamidase regulating pyruvate dehydrogenase complex activity. Cell 159:1615–25 [Google Scholar]
  108. Bao X, Wang Y, Li X, Li XM, Liu Z. 108.  et al. 2014. Identification of ‘erasers’ for lysine crotonylated histone marks using a chemical proteomics approach. eLife 3:e02999 [Google Scholar]
  109. Wiśniewski JR, Zougman A, Mann M. 109.  2008. Nε-formylation of lysine is a widespread post-translational modification of nuclear proteins occurring at residues involved in regulation of chromatin function. Nucl. Acids Res. 36:570–77 [Google Scholar]
  110. Moellering RE, Cravatt BF. 110.  2013. Functional lysine modification by an intrinsically reactive primary glycolytic metabolite. Science 341:549–53 [Google Scholar]
  111. Blander G, Olejnik J, Krzymanska-Olejnik E, McDonagh T, Haigis M. 111.  et al. 2005. SIRT1 shows no substrate specificity in vitro. J. Biol. Chem. 280:9780–85 [Google Scholar]
  112. Rauh D, Fischer F, Gertz M, Lakshminarasimhan M, Bergbrede T. 112.  et al. 2013. An acetylome peptide microarray reveals specificities and deacetylation substrates for all human sirtuin isoforms. Nat. Commun. 4:2327 [Google Scholar]
  113. Garske AL, Denu JM. 113.  2006. SIRT1 top 40 hits: use of one-bead, one-compound acetyl-peptide libraries and quantum dots to probe deacetylase specificity. Biochemistry 45:94–101 [Google Scholar]
  114. AbouElfetouh A, Kuhn ML, Hu LI, Scholle MD, Sorensen DJ. 114.  et al. 2015. The E. coli sirtuin CobB shows no preference for enzymatic and nonenzymatic lysine acetylation substrate sites. MicrobiologyOpen 4:66–83 [Google Scholar]
  115. Smith BC, Settles B, Hallows WC, Craven MW, Denu JM. 115.  2011. SIRT3 substrate specificity determined by peptide arrays and machine learning. ACS Chem. Biol. 6:146–57 [Google Scholar]
  116. Hebert AS, Dittenhafer-Reed KE, Yu W, Bailey DJ, Selen ES. 116.  et al. 2013. Calorie restriction and SIRT3 trigger global reprogramming of the mitochondrial protein acetylome. Mol. Cell 49:186–99 [Google Scholar]
  117. Khan AN, Lewis PN. 117.  2005. Unstructured conformations are a substrate requirement for the Sir2 family of NAD-dependent protein deacetylases. J. Biol. Chem. 280:36073–78 [Google Scholar]
  118. Hirschey MD, Shimazu T, Goetzman E, Jing E, Schwer B. 118.  et al. 2010. SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation. Nature 464:121–25 [Google Scholar]
  119. Bharathi SS, Zhang Y, Mohsen AW, Uppala R, Balasubramani M. 119.  et al. 2013. Sirtuin 3 (SIRT3) protein regulates long-chain acyl-CoA dehydrogenase by deacetylating conserved lysines near the active site. J. Biol. Chem. 288:33837–47 [Google Scholar]
  120. Schwer B, Bunkenborg J, Verdin RO, Andersen JS, Verdin E. 120.  2006. Reversible lysine acetylation controls the activity of the mitochondrial enzyme acetyl-CoA synthetase 2. PNAS 103:10224–29 [Google Scholar]
  121. Kawahara TLA, Michishita E, Adler AS, Damian M, Berber E. 121.  et al. 2009. SIRT6 links histone H3 lysine 9 deacetylation to NF-κB-dependent gene expression and organismal life span. Cell 136:62–74 [Google Scholar]
  122. Zhong L, D'Urso A, Toiber D, Sebastian C, Henry RE. 122.  et al. 2010. The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1α. Cell 140:280–93 [Google Scholar]
  123. Sebastián C, Zwaans BMM, Silberman DM, Gymrek M, Goren A. 123.  et al. 2012. The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. Cell 151:1185–99 [Google Scholar]
  124. Barber MF, Michishita-Kioi E, Xi Y, Tasselli L, Kioi M. 124.  et al. 2012. SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation. Nature 487:114–18 [Google Scholar]
  125. Merrick CJ, Duraisingh MT. 125.  2007. Plasmodium falciparum Sir2: An unusual sirtuin with dual histone deacetylase and ADP-ribosyltransferase activity. Eukaryot. Cell 6:2081–91 [Google Scholar]
  126. Hawse WF, Wolberger C. 126.  2009. Structure-based mechanism of ADP-ribosylation by sirtuins. J. Biol. Chem. 284:33654–61 [Google Scholar]
  127. Fahie K, Hu P, Swatkoski S, Cotter RJ, Zhang Y, Wolberger C. 127.  2009. Side chain specificity of ADP-ribosylation by a sirtuin. FEBS J 276:7159–76 [Google Scholar]
  128. Rack JGM, Morra R, Barkauskaite E, Kraehenbuehl R, Ariza A. 128.  et al. 2015. Identification of a class of protein ADP-ribosylating sirtuins in microbial pathogens. Mol. Cell 59:309–20 [Google Scholar]
  129. Rosenthal F, Feijs KL, Frugier E, Bonalli M, Forst AH. 129.  et al. 2013. Macrodomain-containing proteins are new mono-ADP-ribosylhydrolases. Nat. Struct. Mol. Biol. 20:502–7 [Google Scholar]
  130. Jankevicius G, Hassler M, Golia B, Rybin V, Zacharias M. 130.  et al. 2013. A family of macrodomain proteins reverses cellular mono-ADP-ribosylation. Nat. Struct. Mol. Biol. 20:508–14 [Google Scholar]
  131. Kanfi Y, Naiman S, Amir G, Peshti V, Zinman G. 131.  et al. 2012. The sirtuin SIRT6 regulates lifespan in male mice. Nature 483:218–21 [Google Scholar]
  132. Wagner GR, Payne RM. 132.  2013. Widespread and enzyme-independent Nε-acetylation and Nε-succinylation of proteins in the chemical conditions of the mitochondrial matrix. J. Biol. Chem. 288:29036–45 [Google Scholar]
  133. Ghanta S, Grossmann RE, Brenner C. 133.  2013. Mitochondrial protein acetylation as a cell-intrinsic, evolutionary driver of fat storage: chemical and metabolic logic of acetyl-lysine modifications. Crit. Rev. Biochem. Mol. Biol. 48:561–74 [Google Scholar]
  134. Jiang W, Wang S, Xiao M, Lin Y, Zhou L. 134.  et al. 2011. Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase. Mol. Cell 43:33–44 [Google Scholar]
  135. Marmorstein R. 135.  2001. Structure and function of histone acetyltransferases. Cell. Mol. Life Sci. 58:693–703 [Google Scholar]
  136. Scott I, Webster BR, Li JH, Sack MN. 136.  2012. Identification of a molecular component of the mitochondrial acetyltransferase programme: a novel role for GCN5L1. Biochem. J. 443:655–61 [Google Scholar]
  137. Fan J, Shan C, Kang HB, Elf S, Xie J. 137.  et al. 2014. Tyr phosphorylation of PDP1 toggles recruitment between ACAT1 and SIRT3 to regulate the pyruvate dehydrogenase complex. Mol. Cell 53:534–48 [Google Scholar]
  138. Shan C, Elf S, Ji Q, Kang HB, Zhou L. 138.  et al. 2014. Lysine acetylation activates 6-phosphogluconate dehydrogenase to promote tumor growth. Mol. Cell 55:552–65 [Google Scholar]
  139. Gibson GE, Xu H, Chen HL, Chen W, Denton TT, Zhang S. 139.  2015. Alpha-ketoglutarate dehydrogenase complex-dependent succinylation of proteins in neurons and neuronal cell lines. J. Neurochem. 134:86–96 [Google Scholar]
  140. Hosokawa Y, Shimomura Y, Harris RA, Ozawa T. 140.  1986. Determination of short-chain acyl-coenzyme A esters by high-performance liquid chromatography. Anal. Biochem. 153:45–49 [Google Scholar]
  141. King MT, Reiss PD. 141.  1985. Separation and measurement of short-chain coenzyme-A compounds in rat liver by reversed-phase high-performance liquid chromatography. Anal. Biochem. 146:173–79 [Google Scholar]
  142. Gao L, Chiou W, Tang H, Cheng X, Camp HS, Burns DJ. 142.  2007. Simultaneous quantification of malonyl-CoA and several other short-chain acyl-CoAs in animal tissues by ion-pairing reversed-phase HPLC/MS. J. Chromatogr. B 853:303–13 [Google Scholar]
  143. Cimen H, Han M-J, Yang Y, Tong Q, Koc H, Koc EC. 143.  2010. Regulation of succinate dehydrogenase activity by SIRT3 in mammalian mitochondria. Biochemistry 49:304–11 [Google Scholar]
  144. Finley LWS, Haas W, Desquiret-Dumas V, Wallace DC, Procaccio V. 144.  et al. 2011. Succinate dehydrogenase is a direct target of Sirtuin 3 deacetylase activity. PLOS ONE 6:e23295 [Google Scholar]
  145. Huang R, Holbert MA, Tarrant MK, Curtet S, Colquhoun DR. 145.  et al. 2010. Site-specific introduction of an acetyl-lysine mimic into peptides and proteins by cysteine alkylation. J. Am. Chem. Soc. 132:9986–87 [Google Scholar]
  146. Li F, Allahverdi A, Yang R, Lua GBJ, Zhang X. 146.  et al. 2011. A direct method for site-specific protein acetylation. Angew. Chem. Int. Ed. Engl. 50:9611–14 [Google Scholar]
  147. Neumann H, Peak-Chew SY, Chin JW. 147.  2008. Genetically encoding Nε-acetyllysine in recombinant proteins. Nat. Chem. Biol. 4:232–34 [Google Scholar]
  148. Lammers M, Neumann H, Chin JW, James LC. 148.  2010. Acetylation regulates cyclophilin A catalysis, immunosuppression and HIV isomerization. Nat. Chem. Biol. 6:331–37 [Google Scholar]
  149. Huang Y, Russell WK, Wan W, Pai P-J, Russell DH, Liu W. 149.  2010. A convenient method for genetic incorporation of multiple noncanonical amino acids into one protein in Escherichia coli. Mol. BioSyst. 6:683–86 [Google Scholar]
  150. Yu W, Dittenhafer-Reed KE, Denu JM. 150.  2012. SIRT3 protein deacetylates isocitrate dehydrogenase 2 (IDH2) and regulates mitochondrial redox status. J. Biol. Chem. 287:14078–86 [Google Scholar]
  151. Gattner MJ, Vrabel M, Carell T. 151.  2013. Synthesis of ε-N-propionyl-, ε-N-butyryl-, and ε-N-crotonyl-lysine containing histone H3 using the pyrrolysine system. Chem. Commun. 49:379–81 [Google Scholar]
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