3u3d › Citations

Plasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fatty acyl lysine.

Zhu AY, Zhou Y, Khan S, Deitsch KW, Hao Q, Lin H
ACS Chem Biol 7 155-9 (2012)
Cited: 41 times
EuropePMC logo PMID: 21992006

Abstract

Plasmodium falciparum Sir2A (PfSir2A), a member of the sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylases, has been shown to regulate the expression of surface antigens to evade the detection by host immune surveillance. It is thought that PfSir2A achieves this by deacetylating histones. However, the deacetylase activity of PfSir2A is weak. Here we present enzymology and structural evidence supporting that PfSir2A catalyzes the hydrolysis of medium and long chain fatty acyl groups from lysine residues more efficiently. Furthermore, P. falciparum proteins are found to contain such fatty acyl lysine modifications that can be removed by purified PfSir2A in vitro. Together, the data suggest that the physiological function of PfSir2A in antigen variation may be achieved by removing medium and long chain fatty acyl groups from protein lysine residues. The robust activity of PfSir2A would also facilitate the development of PfSir2A inhibitors, which may have therapeutic value in malaria treatment.

Reviews - 3u3d mentioned but not cited (2)

  1. Modulation of epigenetic targets for anticancer therapy: clinicopathological relevance, structural data and drug discovery perspectives. Andreoli F, Barbosa AJ, Parenti MD, Del Rio A. Curr Pharm Des 19 578-613 (2013)
  2. The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases-Part III: In-Silico Molecular Docking Investigations. Ogungbe IV, Setzer WN. Molecules 21 E1389 (2016)

Articles - 3u3d mentioned but not cited (3)

  1. Kinetic and Structural Basis for Acyl-Group Selectivity and NAD(+) Dependence in Sirtuin-Catalyzed Deacylation. Feldman JL, Dittenhafer-Reed KE, Kudo N, Thelen JN, Ito A, Yoshida M, Denu JM. Biochemistry 54 3037-3050 (2015)
  2. Plasmodium falciparum Sir2A preferentially hydrolyzes medium and long chain fatty acyl lysine. Zhu AY, Zhou Y, Khan S, Deitsch KW, Hao Q, Lin H. ACS Chem Biol 7 155-159 (2012)
  3. Alternate deacylating specificities of the archaeal sirtuins Sir2Af1 and Sir2Af2. Ringel AE, Roman C, Wolberger C. Protein Sci 23 1686-1697 (2014)


Reviews citing this publication (10)

  1. Protein lysine acylation and cysteine succination by intermediates of energy metabolism. Lin H, Su X, He B. ACS Chem Biol 7 947-960 (2012)
  2. Sirtuins in epigenetic regulation. Jing H, Lin H. Chem Rev 115 2350-2375 (2015)
  3. The Substrate Specificity of Sirtuins. Bheda P, Jing H, Wolberger C, Lin H. Annu Rev Biochem 85 405-429 (2016)
  4. The chemical biology of sirtuins. Chen B, Zang W, Wang J, Huang Y, He Y, Yan L, Liu J, Zheng W. Chem Soc Rev 44 5246-5264 (2015)
  5. The Current State of NAD+ -Dependent Histone Deacetylases (Sirtuins) as Novel Therapeutic Targets. Schiedel M, Robaa D, Rumpf T, Sippl W, Jung M. Med Res Rev 38 147-200 (2018)
  6. Biological and catalytic functions of sirtuin 6 as targets for small-molecule modulators. Klein MA, Denu JM. J Biol Chem 295 11021-11041 (2020)
  7. Nutrient-Dependent Changes of Protein Palmitoylation: Impact on Nuclear Enzymes and Regulation of Gene Expression. Spinelli M, Fusco S, Grassi C. Int J Mol Sci 19 E3820 (2018)
  8. A Not-So-Ancient Grease History: Click Chemistry and Protein Lipid Modifications. Suazo KF, Park KY, Distefano MD. Chem Rev 121 7178-7248 (2021)
  9. An update on lysine deacylases targeting the expanding "acylome". Olsen CA. ChemMedChem 9 434-437 (2014)
  10. Lysine Fatty Acylation: Regulatory Enzymes, Research Tools, and Biological Function. Komaniecki G, Lin H. Front Cell Dev Biol 9 717503 (2021)

Articles citing this publication (26)

  1. SIRT6 regulates TNF-α secretion through hydrolysis of long-chain fatty acyl lysine. Jiang H, Khan S, Wang Y, Charron G, He B, Sebastian C, Du J, Kim R, Ge E, Mostoslavsky R, Hang HC, Hao Q, Lin H. Nature 496 110-113 (2013)
  2. Activation of the protein deacetylase SIRT6 by long-chain fatty acids and widespread deacylation by mammalian sirtuins. Feldman JL, Baeza J, Denu JM. J Biol Chem 288 31350-31356 (2013)
  3. Protein Lipidation: Occurrence, Mechanisms, Biological Functions, and Enabling Technologies. Jiang H, Zhang X, Chen X, Aramsangtienchai P, Tong Z, Lin H. Chem Rev 118 919-988 (2018)
  4. Metabolomics-assisted proteomics identifies succinylation and SIRT5 as important regulators of cardiac function. Sadhukhan S, Liu X, Ryu D, Nelson OD, Stupinski JA, Li Z, Chen W, Zhang S, Weiss RS, Locasale JW, Auwerx J, Lin H. Proc Natl Acad Sci U S A 113 4320-4325 (2016)
  5. Efficient demyristoylase activity of SIRT2 revealed by kinetic and structural studies. Teng YB, Jing H, Aramsangtienchai P, He B, Khan S, Hu J, Lin H, Hao Q. Sci Rep 5 8529 (2015)
  6. HAMAP in 2015: updates to the protein family classification and annotation system. Pedruzzi I, Rivoire C, Auchincloss AH, Coudert E, Keller G, de Castro E, Baratin D, Cuche BA, Bougueleret L, Poux S, Redaschi N, Xenarios I, Bridge A. Nucleic Acids Res 43 D1064-70 (2015)
  7. A SIRT2-Selective Inhibitor Promotes c-Myc Oncoprotein Degradation and Exhibits Broad Anticancer Activity. Jing H, Hu J, He B, Negrón Abril YL, Stupinski J, Weiser K, Carbonaro M, Chiang YL, Southard T, Giannakakou P, Weiss RS, Lin H. Cancer Cell 29 297-310 (2016)
  8. Structural and functional analysis of human SIRT1. Davenport AM, Huber FM, Hoelz A. J Mol Biol 426 526-541 (2014)
  9. Identifying the functional contribution of the defatty-acylase activity of SIRT6. Zhang X, Khan S, Jiang H, Antonyak MA, Chen X, Spiegelman NA, Shrimp JH, Cerione RA, Lin H. Nat Chem Biol 12 614-620 (2016)
  10. CPT1A-mediated succinylation of S100A10 increases human gastric cancer invasion. Wang C, Zhang C, Li X, Shen J, Xu Y, Shi H, Mu X, Pan J, Zhao T, Li M, Geng B, Xu C, Wen H, You Q. J Cell Mol Med 23 293-305 (2019)
  11. HDAC8 Catalyzes the Hydrolysis of Long Chain Fatty Acyl Lysine. Aramsangtienchai P, Spiegelman NA, He B, Miller SP, Dai L, Zhao Y, Lin H. ACS Chem Biol 11 2685-2692 (2016)
  12. SIRT6 regulates Ras-related protein R-Ras2 by lysine defatty-acylation. Zhang X, Spiegelman NA, Nelson OD, Jing H, Lin H. Elife 6 e25158 (2017)
  13. Structures, substrates, and regulators of Mammalian sirtuins - opportunities and challenges for drug development. Moniot S, Weyand M, Steegborn C. Front Pharmacol 3 16 (2012)
  14. Inhibitors of the NAD(+)-Dependent Protein Desuccinylase and Demalonylase Sirt5. Maurer B, Rumpf T, Scharfe M, Stolfa DA, Schmitt ML, He W, Verdin E, Sippl W, Jung M. ACS Med Chem Lett 3 1050-1053 (2012)
  15. Expert curation in UniProtKB: a case study on dealing with conflicting and erroneous data. Poux S, Magrane M, Arighi CN, Bridge A, O'Donovan C, Laiho K, UniProt Consortium. Database (Oxford) 2014 bau016 (2014)
  16. SIRT2 and lysine fatty acylation regulate the transforming activity of K-Ras4a. Jing H, Zhang X, Wisner SA, Chen X, Spiegelman NA, Linder ME, Lin H. Elife 6 e32436 (2017)
  17. Chemical probing of the human sirtuin 5 active site reveals its substrate acyl specificity and peptide-based inhibitors. Roessler C, Nowak T, Pannek M, Gertz M, Nguyen GT, Scharfe M, Born I, Sippl W, Steegborn C, Schutkowski M. Angew Chem Int Ed Engl 53 10728-10732 (2014)
  18. SEC-SANS: size exclusion chromatography combined in situ with small-angle neutron scattering. Jordan A, Jacques M, Merrick C, Devos J, Forsyth VT, Porcar L, Martel A. J Appl Crystallogr 49 2015-2020 (2016)
  19. Sirtuin Lipoamidase Activity Is Conserved in Bacteria as a Regulator of Metabolic Enzyme Complexes. Rowland EA, Greco TM, Snowden CK, McCabe AL, Silhavy TJ, Cristea IM. mBio 8 e01096-17 (2017)
  20. Scavengers of reactive γ-ketoaldehydes extend Caenorhabditis elegans lifespan and healthspan through protein-level interactions with SIR-2.1 and ETS-7. Nguyen TT, Caito SW, Zackert WE, West JD, Zhu S, Aschner M, Fessel JP, Roberts LJ. Aging (Albany NY) 8 1759-1780 (2016)
  21. Fluorescence-based screening assays for the NAD⁺-dependent histone deacetylase smSirt2 from Schistosoma mansoni. Schiedel M, Marek M, Lancelot J, Karaman B, Almlöf I, Schultz J, Sippl W, Pierce RJ, Romier C, Jung M. J Biomol Screen 20 112-121 (2015)
  22. Alterations of sirtuins in mitochondrial cytochrome c-oxidase deficiency. Potthast AB, Heuer T, Warneke SJ, Das AM. PLoS One 12 e0186517 (2017)
  23. Comment Biochemistry: Sirtuin on a high-fat diet. Bheda P, Wolberger C. Nature 496 41-42 (2013)
  24. Plasmodium falciparum adapts its investment into replication versus transmission according to the host environment. Abdi AI, Achcar F, Sollelis L, Silva-Filho JL, Mwikali K, Muthui M, Mwangi S, Kimingi HW, Orindi B, Andisi Kivisi C, Alkema M, Chandrasekar A, Bull PC, Bejon P, Modrzynska K, Bousema T, Marti M. Elife 12 e85140 (2023)
  25. Lysine Succinylation of VBS Contributes to Sclerotia Development and Aflatoxin Biosynthesis in Aspergillus flavus. Wang Y, Yang M, Ge F, Jiang B, Hu R, Zhou X, Yang Y, Liu M. Mol Cell Proteomics 22 100490 (2023)
  26. Molecular characterization and in silico evaluation of surfactins produced by endophytic bacteria from Phanera splendens. de Souza EMC, de Oliveira MVD, Siqueira JES, Rocha DCDC, Marinho ADNR, Marinho AMDR, Marinho PSB, Lima AH. Front Chem 11 1240704 (2023)


Quick links