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cGMP production in bacteria

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Abstract

Production of cGMP in bacteria has been studied since the early 1970s. From the beginning on it proved to be a challenging topic. In Escherichia coli the cGMP levels were two orders of magnitude lower than the corresponding cAMP levels. Furthermore, no specific cGMP receptor protein was identified in the bacterium and a physiological role of cGMP in the bacterium was not substantiated. Consequently in 1977, compelling evidence was given that cGMP is a by-product of E. coli adenylate cyclase in vivo. This may be the reason why also work on cGMP in other bacteria like Bacillus licheniformis and Caulobacter crescentus was not pursued any further. However, recent study on cGMP and guanylate cyclase in the cyanobacterium Synechocysis PCC 6803 brought cGMP signaling in bacteria back to attention. In Synechocystis cGMP levels are of similar magnitude as those of cAMP and deletion of the cya2 gene markedly reduced the amount of cGMP without affecting cAMP. A few months ago the Cya2 gene product has been biochemically and structurally characterized. It behaves as a specific guanylate cyclase in vitro and a single amino acid substitution transforms the enzyme into a specific adenylate cyclase. These data point toward the existence of a true bacterial cGMP-signaling pathway, which needs to be explored and established by future experiments.

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References

  1. Kim YR, Kim SK, Kim CM, Lee SE, Rhee JH (2005) Essential role of an adenylate cyclase in regulating Vibrio vulnificus virulence. FEMS Microbiol Lett 243:497–503

    Article  CAS  PubMed  Google Scholar 

  2. Petersen S, Young GM (2002) Essential role for cyclic AMP and its receptor protein in Yersinia enterocolitica virulence. Infect Immun 70:3665–3672

    Article  CAS  PubMed  Google Scholar 

  3. Süsstrunk U, Pidoux J, Taubert S, Ullmann A, Thompson CJ (1998) Pleiotropic effects of cAMP on germination, antibiotic biosynthesis and morphological development in Streptomyces coelicolor. Mol Microbiol 30:33–46

    Article  PubMed  Google Scholar 

  4. Rickman L, Scott C, Hunt DM, Hutchinson T, Menendez MC, Whalan R, Hinds J, Colston MJ, Green J, Buxton RS (2005) A member of the cAMP receptor protein family of transcription regulators in Mycobacterium tuberculosis is required for virulence in mice and controls transcription of the rpfA gene coding for a resuscitation promoting factor. Mol Microbiol 56:1274–1286

    Article  CAS  PubMed  Google Scholar 

  5. Bernlohr RW, Haddox MK, Goldberg ND (1974) Cyclic guanosine 3′:5′-monophosphate in Escherichia coli and Bacillus lichenformis. J Biol Chem 249:4329–4331

    CAS  PubMed  Google Scholar 

  6. Shibuya M, Takebe Y, Kaziro Y (1977) A possible involvement of cya gene in the synthesis of cyclic guanosine 3′:5′-monophosphate in E. coli. Cell 12:521–528

    Article  CAS  PubMed  Google Scholar 

  7. Tao M, Huberman A (1970) Some properties of Escherichia coli adenylate cyclase. Arch Biochem Biophys 141:236–240

    Article  CAS  PubMed  Google Scholar 

  8. Macchia V, Varrone S, Weissbach H, Miller DL, Pastan I (1975) Guanylate cyclase in Escherichia coli. Purification and properties. J Biol Chem 250:6214–6217

    CAS  PubMed  Google Scholar 

  9. Yang JK, Epstein W (1983) Purification and characterization of adenylate cyclase from Escherichia coli K12. J Biol Chem 258:3750–3758

    CAS  PubMed  Google Scholar 

  10. Clark VL, Bernlohr RW (1972) Guanyl cyclase of Bacillus licheniformis. Biochem Biophys Res Commun 46:1570–1575

    Article  CAS  PubMed  Google Scholar 

  11. Barzu O, Danchin A (1994) Adenylyl cyclases: a heterogeneous class of ATP-utilizing enzymes. Prog Nucleic Acid Res Mol Biol 49:241–283

    Article  CAS  PubMed  Google Scholar 

  12. Iyer LM, Aravind L (2002) The catalytic domains of thiamine triphosphatase and CyaB-like adenylyl cyclase define a novel superfamily of domains that bind organic phosphates. BMC Genomics 3:33

    Article  PubMed  Google Scholar 

  13. Dai X-Y, Liu Y, Liang Y-H, Zheng X, Luo M, Li L, Su X-D (2005) Protein expression, crystallization and preliminary X-ray crystallographic studies of YjbK from Bacillus subtilis. Protein Pept Lett 12:663–664

    Article  CAS  PubMed  Google Scholar 

  14. Bhatnagar NB, Bhatnagar R, Venkitasubramanian TA (1984) Characterization and metabolism of cyclic guanosine 3′5′-monophosphate in Mycobacterium smegmatis. Biochem Biophys Res Commun 121:634–640

    Article  CAS  PubMed  Google Scholar 

  15. McCue LA, McDonough KA, Lawrence CE (2000) Functional classification of cNMP-binding proteins and nucleotide cyclases with implications for novel regulatory pathways in Mycobacterium tuberculosis. Genome Res 10:204–219

    Article  CAS  PubMed  Google Scholar 

  16. Sinha SC, Wetterer M, Sprang SR, Schultz JE, Linder JU (2005) Origin of asymmetry in adenylyl cyclases: structures of Mycobacterium tuberculosis Rv1900c. EMBO J 24:663–673

    Article  CAS  PubMed  Google Scholar 

  17. Castro LI, Hermsen C, Schultz JE, Linder JU (2005) Adenylyl cyclase Rv0386 from Mycobacterium tuberculosis H37Rv uses a novel mode for substrate selection. FEBS J 272:3085–3092

    Article  CAS  PubMed  Google Scholar 

  18. Shenoy AR, Sreenath NP, Podobnik M, Kovacevic M, Visweswariah SS (2005) The Rv0805 gene from Mycobacterium tuberculosis encodes a 3′,5′-cyclic nucleotide phosphodiesterase: biochemical and mutational analysis. Biochemistry 44:15695–15704

    Article  CAS  PubMed  Google Scholar 

  19. Keppetipola N, Shuman S (2008) A phosphate-binding histidine of binuclear metallophosphodiesterase enzymes is a determinant of 2′, 3′-cyclic nucleotide phosphodiesterase activity. J Biol Chem 283:30942–30949

    Article  CAS  PubMed  Google Scholar 

  20. Sun IC, Shapiro L, Rosen OM (1974) Purification and characterization of guanylate cyclase from Caulobacter crescentus. Biochem Biophys Res Commun 61:193–203

    Article  CAS  PubMed  Google Scholar 

  21. Sun IC, Shapiro L, Rosen OM (1975) A specific cyclic guanosine 3′:5′-monophosphate-binding protein in Caulobacter crescentus. J Biol Chem 250:6181–6184

    CAS  PubMed  Google Scholar 

  22. Shenoy AR, Visweswariah SS (2004) Class III nucleotide cyclases in bacteria and archaebacteria: lineage-specific expansion of adenylyl cyclases and a dearth of guanylyl cyclases. FEBS Lett 561:11–21

    Article  CAS  Google Scholar 

  23. Ochoa De Alda JA, Ajlani G, Houmard J (2000) Synechocystis strain PCC 6803 cya2, a prokaryotic gene that encodes a guanylyl cyclase. J Bacteriol 182:3839–3842

    Article  CAS  PubMed  Google Scholar 

  24. Rauch A, Leipelt M, Russwurm M, Steegborn C (2008) Crystal structure of the guanylyl cyclase Cya2. Proc Natl Acad Sci USA 105:15720–15725

    Article  CAS  PubMed  Google Scholar 

  25. Taussig R, Quarmby LM, Gilman AG (1993) Regulation of purified type I and type II adenylylcyclases by G protein βγ subunits. J Biol Chem 268:9–12

    CAS  PubMed  Google Scholar 

  26. Tang WJ, Gilman AG (1995) Construction of a soluble adenylyl cyclase activated by Gsα and forskolin. Science 268:1769–1772

    Article  CAS  PubMed  Google Scholar 

  27. Kanacher T, Schultz A, Linder JU, Schultz JE (2002) A GAF-domain-regulated adenylyl cyclase from Anabaena is a self- activating cAMP switch. EMBO J 21:3672–3680

    Article  CAS  PubMed  Google Scholar 

  28. Linder JU, Hammer A, Schultz JE (2004) The effect of HAMP domains on class IIIb adenylyl cyclases from Mycobacterium tuberculosis. Eur J Biochem 271:2446–2451

    Article  CAS  PubMed  Google Scholar 

  29. Ochoa de Alda JA, Houmard J (2000) Genomic survey of cAMP and cGMP signalling components in the cyanobacterium Synechocystis PCC 6803. Microbiology 146:3183–3194

    CAS  PubMed  Google Scholar 

  30. Cadoret J-C, Rousseau B, Perewoska I, Sicora C, Cheregi O, Vass I, Houmard J (2005) Cyclic nucleotides, the photosynthetic apparatus and response to a UV-B stress in the cyanobacterium Synechocystis sp. PCC 6803. J Biol Chem 280:33935–33944

    Article  CAS  PubMed  Google Scholar 

  31. Linder JU (2005) Substrate selection by class III adenylyl cyclases and guanylyl cyclases. IUBMB Life 57:797–803

    Article  CAS  PubMed  Google Scholar 

  32. Tesmer JJ, Sunahara RK, Gilman AG, Sprang SR (1997) Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsα·GTPγS. Science 278:1907–1916

    Article  CAS  PubMed  Google Scholar 

  33. Sunahara RK, Beuve A, Tesmer JJ, Sprang SR, Garbers DL, Gilman AG (1998) Exchange of substrate and inhibitor specificities between adenylyl and guanylyl cyclases. J Biol Chem 273:16332–16338

    Article  CAS  PubMed  Google Scholar 

  34. Tucker CL, Hurley JH, Miller TR, Hurley JB (1998) Two amino acid substitutions convert a guanylyl cyclase, RetGC-1, into an adenylyl cyclase. Proc Natl Acad Sci USA 95:5993–5997

    Article  CAS  PubMed  Google Scholar 

  35. Linder JU, Schultz JE (2003) The class III adenylyl cyclases: multi-purpose signalling modules. Cell Signal 15:1081–1089

    Article  CAS  PubMed  Google Scholar 

  36. Beuve A, Boesten B, Crasnier M, Danchin A, O’Gara F (1990) Rhizobium meliloti adenylate cyclase is related to eukaryotic adenylate and guanylate cyclases. J Bacteriol 172:2614–2621

    CAS  PubMed  Google Scholar 

  37. Beuve A, Krin E, Danchin A (1993) Rhizobium meliloti adenylate cyclase: probing of a NTP-binding site common to cyclases and cation transporters. C R Acad Sci III 316:553–559

    CAS  PubMed  Google Scholar 

  38. Archdeacon J, Talty J, Boesten B, Danchin A, O’Gara F (1995) Cloning of the second adenylate cyclase gene (cya2) from Rhizobium meliloti F34: Sequence similarity to eukaryotic cyclases. FEMS Microbiol Lett 128:177–184

    Article  CAS  PubMed  Google Scholar 

  39. Katayama M, Ohmori M (1997) Isolation and characterization of multiple adenylate cyclase genes from the cyanobacterium Anabaena sp. strain PCC 7120. J Bacteriol 179:3588–3593

    CAS  PubMed  Google Scholar 

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  1. Department of Pharmacology, Weil Medical College of Cornell University, 1300 York Ave, New York, NY, 10065, USA

    Jürgen U. Linder

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Linder, J.U. cGMP production in bacteria. Mol Cell Biochem 334, 215–219 (2010). https://doi.org/10.1007/s11010-009-0321-0

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