Control of Acetyl-coenzyme A Synthetase (AcsA) Activity by Acetylation/deacetylation Without NAD(+) Involvement in Bacillus Subtilis

Overview

Journal J Bacteriol

Publisher American Society for Microbiology

Specialty Microbiology

Date 2006 Jul 21

PMID 16855235

Citations 75

Authors

Jeffrey G Gardner

Frank J Grundy

Tina M Henkin

Jorge C Escalante-Semerena

Affiliations

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Abstract

Posttranslational modification is an efficient mechanism for controlling the activity of structural proteins, gene expression regulators, and enzymes in response to rapidly changing physiological conditions. Here we report in vitro and in vivo evidence that the acuABC operon of the gram-positive soil bacterium Bacillus subtilis encodes a protein acetyltransferase (AcuA) and a protein deacetylase (AcuC), which may control the activity of acetyl-coenzyme A (CoA) synthetase (AMP-forming, AcsA) in this bacterium. Results from in vitro experiments using purified proteins show that AcsA is a substrate for the acetyl-CoA-dependent AcuA acetyltransferase. Mass spectrometry analysis of a tryptic digest of acetylated AcsA (AcsA(Ac)) identified residue Lys549 as the sole modification site in the protein. Unlike sirtuins, the AcuC protein did not require NAD(+) as cosubstrate to deacetylate AcsA(Ac). The function of the putative AcuB protein remains unknown.

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References

Wolfe A . The acetate switch. Microbiol Mol Biol Rev. 2005; 69(1):12-50. PMC: 1082793. DOI: 10.1128/MMBR.69.1.12-50.2005. View

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Miroux B, Walker J . Over-production of proteins in Escherichia coli: mutant hosts that allow synthesis of some membrane proteins and globular proteins at high levels. J Mol Biol. 1996; 260(3):289-98. DOI: 10.1006/jmbi.1996.0399. View

Wach A . PCR-synthesis of marker cassettes with long flanking homology regions for gene disruptions in S. cerevisiae. Yeast. 1996; 12(3):259-65. DOI: 10.1002/(SICI)1097-0061(19960315)12:3%3C259::AID-YEA901%3E3.0.CO;2-C. View

SCHMIEGER H . A method for detection of phage mutants with altered transducing ability. Mol Gen Genet. 1971; 110(4):378-81. DOI: 10.1007/BF00438281. View

Ryu J, Hartin R . Quick transformation in Salmonella typhimurium LT2. Biotechniques. 1990; 8(1):43-5. View

Noirot-Gros M, Dervyn E, Wu L, Mervelet P, Errington J, Ehrlich S . An expanded view of bacterial DNA replication. Proc Natl Acad Sci U S A. 2002; 99(12):8342-7. PMC: 123069. DOI: 10.1073/pnas.122040799. View

Gregoretti I, Lee Y, Goodson H . Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J Mol Biol. 2004; 338(1):17-31. DOI: 10.1016/j.jmb.2004.02.006. View

Gulick A, Starai V, Horswill A, Homick K, Escalante-Semerena J . The 1.75 A crystal structure of acetyl-CoA synthetase bound to adenosine-5'-propylphosphate and coenzyme A. Biochemistry. 2003; 42(10):2866-73. DOI: 10.1021/bi0271603. View

10.

Imai S, ARMSTRONG C, Kaeberlein M, Guarente L . Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase. Nature. 2000; 403(6771):795-800. DOI: 10.1038/35001622. View

11.

Leipe D, Landsman D . Histone deacetylases, acetoin utilization proteins and acetylpolyamine amidohydrolases are members of an ancient protein superfamily. Nucleic Acids Res. 1997; 25(18):3693-7. PMC: 146955. DOI: 10.1093/nar/25.18.3693. View

12.

Grundy F, Waters D, Takova T, Henkin T . Identification of genes involved in utilization of acetate and acetoin in Bacillus subtilis. Mol Microbiol. 1993; 10(2):259-71. DOI: 10.1111/j.1365-2958.1993.tb01952.x. View

13.

Thiagalingam S, Cheng K, Lee H, Mineva N, Thiagalingam A, Ponte J . Histone deacetylases: unique players in shaping the epigenetic histone code. Ann N Y Acad Sci. 2003; 983:84-100. DOI: 10.1111/j.1749-6632.2003.tb05964.x. View

14.

Starai V, Celic I, Cole R, Boeke J, Escalante-Semerena J . Sir2-dependent activation of acetyl-CoA synthetase by deacetylation of active lysine. Science. 2002; 298(5602):2390-2. DOI: 10.1126/science.1077650. View

15.

Shazand K, Frandsen N, Stragier P . Antibiotic-resistance cassettes for Bacillus subtilis. Gene. 1995; 167(1-2):335-6. DOI: 10.1016/0378-1119(95)00652-4. View

16.

SCHMIEGER H, Backhaus H . The origin of DNA in transducing particles in P22-mutants with increased transduction-frequencies (HT-mutants). Mol Gen Genet. 1973; 120(2):181-90. DOI: 10.1007/BF00267246. View

17.

Starai V, Escalante-Semerena J . Acetyl-coenzyme A synthetase (AMP forming). Cell Mol Life Sci. 2004; 61(16):2020-30. PMC: 11138584. DOI: 10.1007/s00018-004-3448-x. View

18.

Landry J, Sutton A, Tafrov S, Heller R, Stebbins J, Pillus L . The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases. Proc Natl Acad Sci U S A. 2000; 97(11):5807-11. PMC: 18515. DOI: 10.1073/pnas.110148297. View

19.

Guzman L, Belin D, CARSON M, Beckwith J . Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter. J Bacteriol. 1995; 177(14):4121-30. PMC: 177145. DOI: 10.1128/jb.177.14.4121-4130.1995. View

20.

Sterner D, Berger S . Acetylation of histones and transcription-related factors. Microbiol Mol Biol Rev. 2000; 64(2):435-59. PMC: 98999. DOI: 10.1128/MMBR.64.2.435-459.2000. View