Skip to main content
SpringerLink
Log in

Nature of the Iron-Oxygen Bond and Control of Oxygen Affinity of the Haem by the Structure of the Globin in Haemoglobin

  • Chapter
Structure and Function Relationships in Biochemical Systems

Part of the book series: Advances in Experimental Medicine and Bioligy ((AEMB,volume 148))

Abstract

Spectroscopic and chemical evidence speak in favour of the iron-oxygen bond being polar. X-ray analysis shows that the oxygen molecule is inclined at an angle of about 115° to the haem plane. Cooperative binding of oxygen by haemoglobin is attributable to an equilibrium between two alternative structures that differ in oxygen affinity by the equivalent of 3–3.5 kcal/mol. The author has proposed that in the low-affinity structure the globin opposes the movement of the iron atom from its pentacoordinated pyramidal geometry in the haem of deoxyhaemoglobin to its hexacoordinated planar geometry in the haem of oxyhaemoglobin, while in the high-affinity structure this restraint is absent. Recent evidence supporting this mechanism is described.

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

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight 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

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

References

  1. L. Pauling and C. Coryell, Magnetic properties and structure of hemoglobin, oxyhemoglobin and carbonmonoxy hemoglobin, Proc. Natl. Acad. Sci. USA 22:210 (1936).

    Article  PubMed  CAS  Google Scholar 

  2. J. J. Weiss, Nature of the iron-oxygen bond in oxyhemoglobin, Nature 202:83 (1964).

    Article  PubMed  CAS  Google Scholar 

  3. H. P. Misra and I. Fridovich, The generation of superoxide radical during the autoxidation of hemoglobin, J. Biol. Chem. 247:6960 (1972).

    PubMed  CAS  Google Scholar 

  4. L. S. Demma and J. K. Salhany, Direct generation of superoxide anions by flash photolysis of human oxyhemoglobin, J. Biol. Chem. 252:1226 (1977).

    PubMed  CAS  Google Scholar 

  5. W. S. Brinigar, C. K. Chang, J. Geibel and T. G. Traylor, Solvent effects on reversible formation and oxidative stability of heme-oxygen complexes, J. Am. Chem. Soc. 96:5597 (1974).

    Article  PubMed  CAS  Google Scholar 

  6. C. H. Barlow, J. C. Maxwell, W. J. Wallace and W. S. Caughey, Elucidation of the mode of binding of oxygen to iron in oxyhemoglobin by infrared spectroscopy, Biochem. Biophys. Res. Commun. 55: 91 (1973).

    Article  CAS  Google Scholar 

  7. A. S. Koster, Electronic state of iron in the oxygen and carbon monoxide adducts of heme proteins, J. Chem. Phys. 63:3284 (1975).

    Article  CAS  Google Scholar 

  8. H. C. Stynes and J. A. Ibers, A pronounced solvent effect on the reversible oxygenation of a cobalt (II) porphyrin system, J. Am. Chem. Soc. 94:5125 (1972).

    Article  PubMed  CAS  Google Scholar 

  9. B. M. Hoffmann and D. H. Petering, Coboglobins: oxygen-carrying cobalt-reconstituted hemoglobin and myoglobin, Proc. Natl. Acad. Sci. USA 67:637 (1970).

    Article  Google Scholar 

  10. J. C. W. Chien and L. C. Dickinson, Electron paramagnetic resonance of single crystal oxycobaltmyoglobin and deoxycobalt-myoglobin, Proc. Natl. Acad. Sci. USA 69:2783 (1972).

    Article  PubMed  CAS  Google Scholar 

  11. T. Yonetani, H. Yamamoto and T. Iizuka, Studies on cobalt myoglobins and hemoglobins III. Electron paramagnetic resonance studies of reversible oxygenation of cobalt myoglobins and hemoglobins, J. Biol. Chem. 249:2168 (1974).

    PubMed  CAS  Google Scholar 

  12. R. K. Gupta, A. S. Mildvan, T. Yonetani and T.S. Strivastava, EPR study of 17O nuclear hyperfine interaction in cobalt-oxyhemoglobin: conformation of bound oxygen, Biochem. Biophys. Res. Commun. 67:1005 (1975).

    Article  CAS  Google Scholar 

  13. J. C. Maxwell and W. S. Caughey, Infrared evidence for similar metal-dioxygen bonding in iron and cobalt oxyhemoglobins, Biochem. Biophys. Res. Commun. 60:1309 (1974).

    Article  PubMed  CAS  Google Scholar 

  14. M. Cerdonio, A. Congiu-Castellano, F. Mogno, B. Pispisa, G. L. Romani and S. Vitale, Magnetic properties of oxyhemoglobin, Proc. Natl. Acad. Sci. USA 74:398 (1977).

    Article  PubMed  CAS  Google Scholar 

  15. M. Cerdonio, A. Congiu-Castellano, L. Calabrese, S. Morante, B. Pispisa, and S. Vitale, Room-temperature magnetic properties of oxy- and carbonmonoxyhemoglobin, Proc. Natl. Acad. Sci. USA 75:4916 (1978).

    Article  PubMed  CAS  Google Scholar 

  16. J. P. Coliman, Synthetic models for the oxygen-binding hemoproteins, Acc. Chem. Res. 10:265 (1977).

    Article  Google Scholar 

  17. S. E. V. Phillips, Structure of oxyhemoglobin, Nature 273:247 (1978).

    Article  PubMed  CAS  Google Scholar 

  18. S. E. V. Phillips, private communication.

    Google Scholar 

  19. G. Fermi, Three-dimensional Fourier synthesis of human deoxy-haemoglobin at 2.5 A resolution: refinement of the atomic model, J. Mol. Biol. 97:237 (1975).

    Article  PubMed  CAS  Google Scholar 

  20. M. F. Perutz, Structure and mechanism of haemoglobin, Br. Med. Bull. 32:237 (1976).

    Google Scholar 

  21. M. F. Perutz, Hemoglobin structure and respiratory transport, Sci. Am. 239:92 (1978).

    Article  PubMed  CAS  Google Scholar 

  22. M. F. Perutz, Regulation of oxygen affinity of hemoglobin: influence of structure of the globin on the heme iron, Ann. Rev. Biochem. 48:327 (1979).

    Article  PubMed  CAS  Google Scholar 

  23. J. M. Baldwin, Structure and function of hemoglobin, Prog. Biophys. Mol. Biol. 29:225 (1975).

    Article  CAS  Google Scholar 

  24. M. F. Perutz, Stereochemistry of cooperative effects in haemoglobin, Nature 228:726 (1970).

    Article  PubMed  CAS  Google Scholar 

  25. M. F. Perutz, Nature of haem-haem interaction, Nature, 237:495 (1972).

    Article  PubMed  CAS  Google Scholar 

  26. Q. H. Gibson, The photochemical formation of a quickly reacting form of haemoglobin, Biochem. J. 71: 293 (1959).

    PubMed  CAS  Google Scholar 

  27. M. Brunori, E. Antonini, J. Wyman, and S. R. Anderson, Spectral differences between haemoglobin and isolated haemoglobin chains in the deoxygenated state, J. Mol. Biol. 34: 357 (1968).

    Article  CAS  Google Scholar 

  28. M. F. Perutz, J. E. Ladner, S. E. Simon and C. Ho, Influence of globin structure on the state of the heme. I. Human deoxyhemoglobin, Biochemistry 13:2163 (1974).

    Article  PubMed  CAS  Google Scholar 

  29. Y. Sugita, Differences in spectra of α and ß chains of hemoglobin between isolated state and in tetramer, J. Biol. Chem. 250:1251 (1975).

    PubMed  CAS  Google Scholar 

  30. M. F. Perutz, E. J. Heidner, J. E. Ladner, J. G. Beetlestone, C. Ho and E. F. Slade, Influence of globin structure on the state of the heme. III. Changes in heme spectra accompanying allosteric transitions in methemoglobin and their implications for the heme-heme interaction, Biochemistry 13:2187 (1974).

    Article  PubMed  CAS  Google Scholar 

  31. K. Nagai and T. Kitagawa, Differences in Fe(II)-Nε (His-F8) stretching frequencies between deoxyhemoglobins in the two alternative quaternary structures, Proc. Natl. Acad. Sci. USA 77:2033 (1980).

    Article  PubMed  CAS  Google Scholar 

  32. A. Desbois, M. Lutz and R. Banerjee, Low-frequency vibrations in resonance Raman spectra of horse heart myoglobin. Iron-ligand and iron-nitrogen vibrational modes, Biochemistry 18:1510 (1979).

    Article  PubMed  CAS  Google Scholar 

  33. H. Hori and T. Kitagawa, Iron ligand stretching band in the resonance Raman spectra of ferrous iron porphyrin derivatives. Importance as a probe band for quaternary structure of hemoglobin, J. Am. Chem. Soc. 102:3608 (1980).

    Article  CAS  Google Scholar 

  34. J.A. Shelnutt, D. L. Rousseau, J. L. Friedman and S. R. Simon, Protein-heme interaction in hemoglobin: evidence from Raman difference spectroscopy, Proc. Natl. Acad. Sci. USA 76: 4409 (1979).

    Article  PubMed  CAS  Google Scholar 

  35. M. F. Perutz, J. V. Kilmartin, K. Nagai and S. R. Simon, Influence of globin structures on the state of heme. Ferrous low spin derivatives, Biochemistry 15: 378 (1976).

    Article  PubMed  CAS  Google Scholar 

  36. R. C. Cassoly, Relation between optical absorption spectrum and structure of nitrosylhemoglobin, R. Acad. Sci. Ser. D. 278: 1417 (1974).

    CAS  Google Scholar 

  37. J.C. Maxwell and W. S. Caughey, An infrared study of NO bonding to heme B and hemoglobin A. Evidence for inositol hexaphos-phate induced cleavage of proximal histidine to iron bonds, Biochemistry 15: 388 (1976).

    Article  PubMed  CAS  Google Scholar 

  38. A. Szabo and M. F. Perutz, Equilibrium between six- and five-coordinated hemes in nitrosylhemoglobin: interpretation of electron spin resonance spectra, Biochemistry 15: 4427 (1976).

    Article  PubMed  CAS  Google Scholar 

  39. A. Szabo and L. B. Barron, Resonance Raman studies of nitric oxide hemoglobin, J. Am. Chem. Soc. 97: 660 (1975).

    Article  PubMed  CAS  Google Scholar 

  40. J. D. Stong, J. M. Burke, P. Daly, P. Wright and T. G. Spiro, Resonance Raman spectra of nitrosyl heme proteins and of porphyrin analogues, J. Am. Chem. Soc. 102: 5815 (1980).

    Article  CAS  Google Scholar 

  41. J. M. Salhany, S. Ogawa, and R. G. Shulman, Spectral-kinetic heterogeneity in reactions of nitrosyl hemoglobin, Proc. Natl. Acad. Sci. USA 71: 3359 (1974).

    Article  PubMed  CAS  Google Scholar 

  42. J. M. Salhany, S. Ogawa, and R.G. Shulman, Correlation between quaternary structure and ligand dissociation kinetics for fully liganded hemoglobin, Biochemistry 14: 2180 (1975).

    Article  PubMed  CAS  Google Scholar 

  43. M. F. Perutz, J. K. M. Sanders, D. H. Chenery, R. W. Noble, R. R. Pennelly, L. W. Fung, C. Ho, I. Giannini, D. Pörschke and H. Winkler, Interactions between the quaternary structure of the globin and the spin state of the heme in ferric mixed spin derivatives of hemoglobin, Biochemistry 17:3640 (1978).

    Article  PubMed  CAS  Google Scholar 

  44. C. Messana, M. Cerdonio, P. Shenkin, R. W. Noble, G. Fermi, R. N. Perutz and M. F. Perutz, Influence of quaternary structure of the globin on thermal spin equilibria in different methemoglobin derivatives, Biochemistry 17:3652 (1978).

    Article  PubMed  CAS  Google Scholar 

  45. T. Iizuka and T. Yonetani, Spin changes in hemoproteins Adv. Biophys. 1: 157 (1970).

    PubMed  CAS  Google Scholar 

  46. D. M. Sholler and B. M. Hoffmann, Resonance Raman and electron paramagnetic resonance studies of the quaternary structure change in carp hemoglobin. Sensitivity of these spectroscopic probes to heme strain, J. Am. Chem. Soc. 101: 1655 (1979).

    Article  Google Scholar 

  47. M. Rougee and D. Brault, Influence of trans weak or strongfield ligands upon the affinity of deuteroheme for carbon monoxide. Monoimidazole heme as a reference for unconstrained five-coordinate hemoproteins, Biochemistry 14: 4100 (1975).

    Article  CAS  Google Scholar 

  48. J. P. Coliman, J. J. Brauman, K. M. Dowsee, T. R. Haibert, S. E. Hayes and K. S. Suslick, Oxygen binding to cobalt porphyrins, J. Am. Chem. Soc. 100: 2761 (1978).

    Article  Google Scholar 

  49. J. P. Coliman, J. J. Brauman, K. M. Dowsee, T. R. Halbert and K. S. Suslick, Model compounds for the T state of hemoglobin, Proc. Natl. Acad. Sci. USA 75: 564 (1978).

    Article  Google Scholar 

  50. J. Geibel, J. Cannon, D. Campbell and T. G. Traylor, Model compounds for R-state and T-state hemoglobins, J. Am. Chem. Soc. 100: 3575 (1978).

    Article  CAS  Google Scholar 

  51. D. K. White, J. B. Cannon, and T. G. Traylor, A kinetic model for R-state and T-state hemoglobin. Flash photolysis of heme-imidazole-carbon monoxide mixtures, J. Am. Chem. Soc. 101: 2443 (1979).

    Article  CAS  Google Scholar 

  52. A. Warshel, Energy-structure correlation in metalloporphyrins and the control of oxygen binding by hemoglobin, Proc. Natl. Acad. Sci. USA 74: 1789 (1977).

    Article  PubMed  CAS  Google Scholar 

  53. J. L. Hoard, private communication.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Research Council, Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, England

    M. F. Perutz

Authors
  1. M. F. Perutz
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Rome, Rome, Italy

    Francesco Bossa , Alessandro Finazzi-Agrò  & Roberto Strom ,  & 

  2. CNR Center of Molecular Biology, Rome, Italy

    Emilia Chiancone

Rights and permissions

Reprints and permissions

Copyright information

© 1982 Plenum Press, New York

About this chapter

Cite this chapter

Perutz, M.F. (1982). Nature of the Iron-Oxygen Bond and Control of Oxygen Affinity of the Haem by the Structure of the Globin in Haemoglobin. In: Bossa, F., Chiancone, E., Finazzi-Agrò, A., Strom, R. (eds) Structure and Function Relationships in Biochemical Systems. Advances in Experimental Medicine and Bioligy, vol 148. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-9281-5_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-9281-5_4

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4615-9283-9

  • Online ISBN: 978-1-4615-9281-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation