Skip to main content
SpringerLink
Log in
Book cover

cGMP: Generators, Effectors and Therapeutic Implications pp 17–31Cite as

Biochemistry of Soluble Guanylate Cyclase

  • Chapter

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 191))

Abstract

Nitric oxide (NO) functions in biology as both a critical cytotoxic agent and an essential signaling molecule. The toxicity of the diatomic gas has long been accepted; however, it was not known to be a signaling molecule until it was identified as the endothelium-derived relaxing factor (EDRF). Since this discovery, the physiological signaling pathways that are regulated by NO have been the focus of numerous studies. Many of the cellular responses that NO modulates are mediated by the heme protein soluble guanylate cyclase (sGC). NO binds to sGC at a diffusion controlled rate, and leads to a several 100-fold increase in the synthesis of the second messenger cGMP from GTP. Other diatomic gases either do not bind (dioxygen), or do not significantly activate (carbon monoxide) sGC. This provides selectivity and efficiency for NO even in an aerobic environment, which is critical due to the high reactivity of NO. Several biochemical studies have focused on elucidating the mechanism of NO activation and O2 discrimination. Significant advances in our understanding of these topics have occurred with the identification and characterization of the sGC-like homologues termed Heme-Nitric oxide and OXygen binding (H-NOX) proteins.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   329.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Alderton WK, Cooper CE, Knowles RG (2001) Nitric oxide synthases: structure, function and inhibition. Biochem J 357:593–615

    Article  PubMed  CAS  Google Scholar 

  • Artz JD, Schmidt B, McCracken JL, Marletta MA (2002) Effects of nitroglycerin on soluble guany-late cyclase: implications for nitrate tolerance. J Biol Chem 277:18253–18256

    Article  PubMed  CAS  Google Scholar 

  • Behrends S, Harteneck C, Schultz G, Koesling D (1995) A variant of the alpha 2 subunit of soluble guanylyl cyclase contains an insert homologous to a region within adenylyl cyclases and functions as a dominant negative protein. J Biol Chem 270:21109–21113

    Article  PubMed  CAS  Google Scholar 

  • Bellingham M, Evans TJ (2007) The alpha2beta1 isoform of guanylyl cyclase mediates plasma membrane localized nitric oxide signalling. Cell Signal 19:2183–2193

    Article  PubMed  CAS  Google Scholar 

  • Boon EM, Huang SH, Marletta MA (2005) A molecular basis for NO selectivity in soluble guany-late cyclase. Nat Chem Biol 1:53–59

    Article  PubMed  CAS  Google Scholar 

  • Boon EM, Marletta MA (2005) Ligand specificity of H-NOX domains: from sGC to bacterial NO sensors. J Inorg Biochem 99:892–902

    Article  PubMed  CAS  Google Scholar 

  • Bredt DS (1999) Endogenous nitric oxide synthesis: biological functions and pathophysiology. Free Radic Res 31:577–596

    Article  PubMed  CAS  Google Scholar 

  • Budworth J, Meillerais S, Charles I, Powell K (1999) Tissue distribution of the human soluble guanylate cyclases. Biochem Biophys Res Commun 263:696–701

    Article  PubMed  CAS  Google Scholar 

  • Cary SP, Winger JA, Marletta MA (2005) Tonic and acute nitric oxide signaling through soluble guanylate cyclase is mediated by nonheme nitric oxide, ATP, and GTP. Proc Natl Acad Sci USA 102:13064–13069

    Article  PubMed  CAS  Google Scholar 

  • Cary SP, Winger JA, Derbyshire ER, Marletta MA (2006) Nitric oxide signaling: no longer simply on or off. Trends Biochem Sci 31:231–239

    Article  PubMed  CAS  Google Scholar 

  • Deinum G, Stone JR, Babcock GT, Marletta MA (1996) Binding of nitric oxide and carbon monoxide to soluble guanylate cyclase as observed with resonance Raman spectroscopy. Biochemistry 35:1540–1547

    Article  PubMed  CAS  Google Scholar 

  • Derbyshire ER, Marletta MA (2007) Butyl isocyanide as a probe of the activation mechanism of soluble guanylate cyclase: investigating the role of non-heme nitric oxide. J Biol Chem 282:35741–35748

    Article  PubMed  CAS  Google Scholar 

  • Derbyshire ER, Tran R, Mathies RA, Marletta MA (2005) Characterization of nitrosoalkane binding and activation of soluble guanylate cyclase. Biochemistry 44:16257–16265

    Article  PubMed  CAS  Google Scholar 

  • Derbyshire ER, Gunn A, Ibrahim M, Spiro TG, Britt RD, Marletta MA (2008) Characterization of two different five-coordinate soluble guanylate cyclase ferrous-nitrosyl complexes. Biochemistry 47:3892–3899

    Article  PubMed  CAS  Google Scholar 

  • Dierks EA, Burstyn JN (1998) The deactivation of soluble guanylyl cyclase by redox-active agents. Arch Biochem Biophys 351:1–7

    Article  PubMed  CAS  Google Scholar 

  • Dudzinski DM, Igarashi J, Greif D, Michel T (2006) The regulation and pharmacology of endothe-lial nitric oxide synthase. Annu Rev Pharmacol Toxicol 46:235–276

    Article  PubMed  CAS  Google Scholar 

  • Evgenov OV, Pacher P, Schmidt PM, Hasko G, Schmidt HHHW, Stasch JP (2006) NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential. Nat Rev Drug Discov 5:755–768

    Article  PubMed  CAS  Google Scholar 

  • Friebe A, Schultz G, Koesling D (1996) Sensitizing soluble guanylyl cyclase to become a highly CO-sensitive enzyme. EMBO J 15:6863–6868

    PubMed  CAS  Google Scholar 

  • Friebe A, Mergia E, Dangel O, Lange A, Koesling D (2007) Fatal gastrointestinal obstruction and hypertension in mice lacking nitric oxide-sensitive guanylyl cyclase. Proc Natl Acad Sci USA 104:7699–7704

    Article  PubMed  CAS  Google Scholar 

  • Garthwaite J, Southam E, Boulton CL, Nielsen EB, Schmidt K, Mayer B (1995) Potent and selective inhibition of nitric oxide-sensitive guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one. Mol Pharmacol 48:184–188

    PubMed  CAS  Google Scholar 

  • Gray JM, Karow DS, Lu H, Chang AJ, Chang JS, Ellis RE, Marletta MA, Bargmann CI (2004) Oxygen sensation and social feeding mediated by a C. elegans guanylate cyclase homologue. Nature 430:317–322

    Article  PubMed  CAS  Google Scholar 

  • Harteneck C, Wedel B, Koesling D, Malkewitz J, Bohme E, Schultz G (1991) Molecular cloning and expression of a new alpha-subunit of soluble guanylyl cyclase: interchangeability of the alpha-subunits of the enzyme. FEBS Lett 292:217–222

    Article  PubMed  CAS  Google Scholar 

  • Huang SH, Rio DC, Marletta MA (2007) Ligand binding and inhibition of an oxygen-sensitive soluble guanylate cyclase, Gyc-88E, from Drosophila. Biochemistry 46:15115–15122

    Article  PubMed  CAS  Google Scholar 

  • Ignarro LJ, Wood KS, Wolin MS (1982) Activation of purified soluble guanylate cyclase by proto-porphyrin IX. Proc Natl Acad Sci USA 79:2870–2873

    Article  PubMed  CAS  Google Scholar 

  • Iyer LM, Anantharaman V, Aravind L (2003) Ancient conserved domains shared by animal soluble guanylyl cyclases and bacterial signaling proteins. BMC Genomics 4:5

    Article  PubMed  Google Scholar 

  • Jain R, Chan MK (2003) Mechanisms of ligand discrimination by heme proteins. J Biol Inorg Chem 8:1–11

    Article  PubMed  CAS  Google Scholar 

  • Karow DS, Pan D, Davis JH, Behrends S, Mathies RA, Marletta MA (2005) Characterization of functional heme domains from soluble guanylate cyclase. Biochemistry 44:16266–16274

    Article  PubMed  CAS  Google Scholar 

  • Kelley LA, MacCallum RM, Sternberg MJ (2000) Enhanced genome annotation using structural profiles in the program 3D-PSSM. J Mol Biol 299:499–520

    Article  PubMed  CAS  Google Scholar 

  • Kharitonov VG, Russwurm M, Magde D, Sharma VS, Koesling D (1997) Dissociation of nitric oxide from soluble guanylate cyclase. Biochem Bioph Res Co 239:284–286

    Article  CAS  Google Scholar 

  • Kharitonov VG, Sharma VS, Magde D, Koesling D (1999) Kinetics and equilibria of soluble guanylate cyclase ligation by CO: effect of YC-1. Biochemistry 38:10699–10706

    Article  PubMed  CAS  Google Scholar 

  • Ko FN, Wu CC, Kuo SC, Lee FY, Teng CM (1994) YC-1, a novel activator of platelet guanylate cyclase. Blood 84:4226–4233

    PubMed  CAS  Google Scholar 

  • Koglin M, Vehse K, Budaeus L, Scholz H, Behrends S (2001) Nitric oxide activates the beta 2 subunit of soluble guanylyl cyclase in the absence of a second subunit. J Biol Chem 276:30737–30743

    Article  PubMed  CAS  Google Scholar 

  • Li ZQ, Pal B, Takenaka S, Tsuyama S, Kitagawa T (2005) Resonance Raman evidence for the presence of two heme pocket conformations with varied activities in CO-bound bovine soluble guanylate cyclase and their conversion. Biochemistry 44:939–946

    Article  PubMed  CAS  Google Scholar 

  • Ma X, Sayed N, Beuve A, van den Akker F (2007) NO and CO differentially activate soluble guanylyl cyclase via a heme pivot-bend mechanism. EMBO J 26:578–588

    Article  PubMed  CAS  Google Scholar 

  • Ma X, Sayed N, Baskaran P, Beuve A, van den Akker F (2008) PAS-mediated dimerization of soluble guanylyl cyclase revealed by signal transduction histidine kinase domain crystal structure. J Biol Chem 283:1167–1178

    Article  PubMed  CAS  Google Scholar 

  • Makino R, Obayashi E, Homma N, Shiro Y, Hori H (2003) YC-1 facilitates release of the proximal His residue in the NO and CO complexes of soluble guanylate cyclase. J Biol Chem 278:11130–11137

    Article  PubMed  CAS  Google Scholar 

  • Martin E, Czarnecki K, Jayaraman V, Murad F, Kincaid J (2005) Resonance Raman and infrared spectroscopic studies of high-output forms of human soluble guanylyl cyclase. J Am Chem Soc 127:4625–4631

    Article  PubMed  CAS  Google Scholar 

  • Martin E, Berka V, Bogatenkova E, Murad F, Tsai A L (2006) Ligand selectivity of soluble guanylyl cyclase - effect of the hydrogen-bonding tyrosine in the distal heme pocket on binding of oxygen, nitric oxide, and carbon monoxide. J Biol Chem 281:27836–27845

    Article  PubMed  CAS  Google Scholar 

  • Morishita T, Tsutsui M, Shimokawa H, Sabanai K, Tasaki H, Suda O, Nakata S, Tanimoto A, Wang KY, Ueta Y, Sasaguri Y, Nakashima Y, Yanagihara N (2005) Nephrogenic diabetes insipidus in mice lacking all nitric oxide synthase isoforms. Proc Natl Acad Sci USA 102:10616–10621

    Article  PubMed  CAS  Google Scholar 

  • Morton DB (2004) Atypical soluble guanylyl cyclases in Drosophila can function as molecular oxygen sensors. J Biol Chem 279:50651–50653

    Article  PubMed  CAS  Google Scholar 

  • Morton DB, Langlais KK, Stewart JA, Vermehren A (2005) Comparison of the properties of the five soluble guanylyl cyclase subunits in Drosophila melanogaster. J Insect Sci 5:12

    PubMed  Google Scholar 

  • Mulsch A, Busse R, Liebau S, Forstermann U (1988) LY 83583 interferes with the release of endothelium-derived relaxing factor and inhibits soluble guanylate cyclase. J Pharmacol Exp Ther 247:283–288

    PubMed  CAS  Google Scholar 

  • Munzel T, Feil R, Mulsch A, Lohmann SM, Hofmann F, Walter U (2003) Physiology and pathophysiology of vascular signaling controlled by cyclic guanosine 3′,5′-cyclic monophosphate-dependent protein kinase. Circulation 108:2172–2183

    Article  PubMed  Google Scholar 

  • Nioche P, Berka V, Vipond J, Minton N, Tsai AL, Raman CS (2004) Femtomolar sensitivity of a NO sensor from Clostridium botulinum. Science 306:1550–1553

    Article  PubMed  CAS  Google Scholar 

  • Pellicena P, Karow DS, Boon EM, Marletta MA, Kuriyan J (2004) Crystal structure of an oxygen-binding heme domain related to soluble guanylate cyclases. Proc Natl Acad Sci USA 101:12854–12859

    Article  PubMed  CAS  Google Scholar 

  • Price MS, Chao LY, Marletta MA (2007) Shewanella oneidensis MR-1 H-NOX regulation of a histidine kinase by nitric oxide. Biochemistry 46:13677–13683

    Article  PubMed  CAS  Google Scholar 

  • Rothkegel C, Schmidt PM, Atkins DJ, Hoffmann LS, Schmidt HH, Schroder H, Stasch JP (2007) Dimerization region of soluble guanylate cyclase characterized by bimolecular fluorescence complementation in vivo. Mol Pharmacol 72:1181–1190

    Article  PubMed  CAS  Google Scholar 

  • Ruiz-Stewart I, Tiyyagura SR, Lin JE, Kazerounian S, Pitari GM, Schulz S, Martin E, Murad F, Waldman SA (2004) Guanylyl cyclase is an ATP sensor coupling nitric oxide signaling to cell metabolism. Proc Natl Acad Sci USA 101:37–42

    Article  PubMed  CAS  Google Scholar 

  • Russwurm M, Behrends S, Harteneck C, Koesling D (1998) Functional properties of a naturally occurring isoform of soluble guanylyl cyclase. Biochem J 335(Pt 1):125–130

    PubMed  CAS  Google Scholar 

  • Russwurm M, Koesling D (2004) NO activation of guanylyl cyclase. EMBO J 23:4443–4450

    Article  PubMed  CAS  Google Scholar 

  • Sanders KM, Ward SM, Thornbury KD, Dalziel HH, Westfall DP, Carl A (1992) Nitric-oxide as a nonadrenergic, noncholinergic neurotransmitter in the gastrointestinal-tract. Jpn J Pharmacol 58:220–225

    Google Scholar 

  • Sayed N, Baskaran P, Ma X, van den Akker F, Beuve A (2007) Desensitization of soluble guanylyl cyclase, the NO receptor, by S-nitrosylation. Proc Natl Acad Sci USA 104:12312–12317

    Article  PubMed  CAS  Google Scholar 

  • Shiga T, Suzuki N (2005) Amphipathic alpha-helix mediates the heterodimerization of soluble guanylyl cyclase. Zoolog Sci 22:735–742

    Article  PubMed  CAS  Google Scholar 

  • Stone JR, Marletta MA (1994) Soluble guanylate cyclase from bovine lung: activation with nitric oxide and carbon monoxide and spectral characterization of the ferrous and ferric states. Biochemistry 33:5636–5640

    Article  PubMed  CAS  Google Scholar 

  • Stone JR, Marletta MA (1995) The ferrous heme of soluble guanylate cyclase: formation of hex-acoordinate complexes with carbon monoxide and nitrosomethane. Biochemistry 34:16397– 16403

    Article  PubMed  CAS  Google Scholar 

  • Stone JR, Marletta MA (1996) Spectral and kinetic studies on the activation of soluble guanylate cyclase by nitric oxide. Biochemistry 35:1093–1099

    Article  PubMed  CAS  Google Scholar 

  • Stone JR, Marletta MA (1998) Synergistic activation of soluble guanylate cyclase by YC-1 and carbon monoxide: implications for the role of cleavage of the iron-histidine bond during activation by nitric oxide. Chem Biol 5:255–261

    Article  CAS  Google Scholar 

  • Stuehr DJ (1997) Structure-function aspects in the nitric oxide synthases. Annu Rev Pharmacol 37:339–359

    Article  CAS  Google Scholar 

  • Sunahara RK, Tesmer JJG, Gilman AG, Sprang SR (1997) Crystal structure of the adenylyl cyclase activator G(S alpha). Science 278:1943–1947

    Article  PubMed  CAS  Google Scholar 

  • Tomita T, Ogura T, Tsuyama S, Imai Y, Kitagawa T (1997) Effects of GTP on bound nitric oxide of soluble guanylate cyclase probed by resonance Raman spectroscopy. Biochemistry 36:10155– 10160

    Article  PubMed  CAS  Google Scholar 

  • Traut TW (1994) Physiological concentrations of purines and pyrimidines. Mol Cell Biochem 140:1–22

    Article  PubMed  CAS  Google Scholar 

  • Vermeersch P, Buys E, Pokreisz P, Marsboom G, Ichinose F, Sips P, Pellens M, Gillijns H, Swinnen M, Graveline A, Collen D, Dewerchin M, Brouckaert P, Bloch KD, Janssens S (2007) Soluble guanylate cyclase-alpha1 deficiency selectively inhibits the pulmonary vasodilator response to nitric oxide and increases the pulmonary vascular remodeling response to chronic hypoxia. Circulation 116:936–943

    Article  PubMed  CAS  Google Scholar 

  • Warner TD, Mitchell JA, Sheng H, Murad F (1994) Effects of cyclic GMP on smooth muscle relaxation. Adv Pharmacol 26:171–194

    Article  PubMed  CAS  Google Scholar 

  • Wedel B, Humbert P, Harteneck C, Foerster J, Malkewitz J, Bohme E, Schultz G, Koesling D (1994) Mutation of His-105 in the β1 subunit yields a nitric oxide-insensitive form of soluble guanylyl cyclase. Proc Natl Acad Sci USA 91:2592–2596

    Article  PubMed  CAS  Google Scholar 

  • Wedel B, Harteneck C, Foerster J, Friebe A, Schultz G, Koesling D (1995) Functional domains of soluble guanylyl cyclase. J Biol Chem 270:24871–24875

    Article  PubMed  CAS  Google Scholar 

  • Winger JA (2004) Activation and deactivation of soluble guanylate cyclase: Domain organization and the requirement for non-heme equivalents of nitric oxide. Ph. D. Dissertation, The University of Michigan

    Google Scholar 

  • Winger JA, Marletta MA (2005) Expression and characterization of the catalytic domains of soluble guanylate cyclase: interaction with the heme domain. Biochemistry 44:4083–4090

    Article  PubMed  CAS  Google Scholar 

  • Winger JA, Derbyshire ER, Marletta MA (2006) Dissociation of nitric oxide from soluble guany-late cyclase and H-NOX domain constructs. J Biol Chem 282:897–907

    Article  PubMed  Google Scholar 

  • Yuen PS, Potter LR, Garbers DL (1990) A new form of guanylyl cyclase is preferentially expressed in rat kidney. Biochemistry 29:10872–10878

    Article  PubMed  CAS  Google Scholar 

  • Zhang GY, Liu Y, Ruoho AE, Hurley JH (1997) Structure of the adenylyl cyclase catalytic core. Nature 386:247–253

    Article  PubMed  CAS  Google Scholar 

  • Zhao Y, Marletta MA (1997) Localization of the heme binding region in soluble guanylate cyclase. Biochemistry 36:15959–15964

    Article  PubMed  CAS  Google Scholar 

  • Zhao Y, Brandish PE, Ballou DP, Marletta MA (1999) A molecular basis for nitric oxide sensing by soluble guanylate cyclase. Proc Natl Acad Sci USA 96:14753–14758

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. University of California, Berkeley, USA

    Emily R. Derbyshire & Michael A. Marletta

Authors
  1. Emily R. Derbyshire
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael A. Marletta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael A. Marletta .

Editor information

Editors and Affiliations

  1. Dept. Pharmacology, Monash University, Wellington Road, Clayton, VIC, 3800, Australia

    Harald H. H. W. Schmidt

  2. Inst. Pharmakologie und Toxikologie, TU München, Biedersteiner Str. 29, München, 80802, Germany

    Franz Hofmann

  3. Bayer Schering Pharma AG Cardiology Research, Pharma Research Center, Wuppertal, 42096, Germany

    Johannes-Peter Stasch

Rights and permissions

Reprints and permissions

Copyright information

© 2009 Springer

About this chapter

Cite this chapter

Derbyshire, E.R., Marletta, M.A. (2009). Biochemistry of Soluble Guanylate Cyclase. In: Schmidt, H.H.H.W., Hofmann, F., Stasch, JP. (eds) cGMP: Generators, Effectors and Therapeutic Implications. Handbook of Experimental Pharmacology, vol 191. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-68964-5_2

Download citation

Publish with us

Policies and ethics

Search

Navigation