Skip to main content
SpringerLink
Log in

Kinetics of cyanide and carbon monoxide dissociation from ferrous human haptoglobin:hemoglobin(II) complexes

  • Original Paper
  • Published:
JBIC Journal of Biological Inorganic Chemistry Aims and scope Submit manuscript

Abstract

Haptoglobin (Hp) counterbalances the adverse effects of extra-erythrocytic hemoglobin (Hb) trapping the αβ dimers of Hb. In turn, the Hp:Hb complexes display heme-based reactivity. Here, the kinetics of cyanide and carbon monoxide dissociation from ferrous-ligated Hp:Hb complexes are reported at pH 7.0 and 20.0 °C. Cyanide dissociation from Hp1-1:Hb(II)-CN− and Hp2-2:Hb-CN− has been followed upon the dithionite-mediated conversion of ferric to ferrous-ligated Hp:Hb complexes. Values of kon for the dithionite-mediated reduction of Hp1-1:Hb(III)-CN− and Hp2-2:Hb(III)-CN− are (7.3 ± 1.1) × 106 M−1 s−1 and (6.2 ± 1.0) × 106 M−1 s−1, respectively. Values of the first-order rate constant (i.e., h) for cyanide dissociation from Hp1-1:Hb(II)-CN− and Hp2-2:Hb(II)-CN− are (1.2 ± 0.2) × 10−1 s−1 and (1.3 ± 0.2) × 10−1 s−1, respectively. CO dissociation from Hp:Hb(II)-CO complexes has been followed by replacing CO with NO. Values of the first-order rate constant (i.e., l) for CO dissociation from Hp1-1:Hb(II)-CO are (1.4 ± 0.2) × 10−2 s−1 and (6.2 ± 0.8) × 10−3 s−1, and those from Hp2-2:Hb(II)-CO are (1.3 ± 0.2) × 10−2 s−1 and (7.3 ± 0.9) × 10−3 s−1. Values of kon, h, and l correspond to those reported for the R-state of tetrameric Hb and isolated α and β chains. This highlights the view that the conformation of the Hb αβ-dimers bound to Hp1-1 and Hp2-2 matches that of the R-state of the Hb tetramer. Furthermore, unlike ferric Hb(III), ligated ferrous Hb(II) does not show an assembly-linked structural change.

Graphic abstract

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Scheme 2
Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

CCP domain:

Complement control protein domain

CO:

Carbon monoxide

Hb:

Human hemoglobin

Hb(III):

Ferric Hb

Hb(II):

Ferrous Hb

Hp:

Human haptoglobin

Hp1-1:

Phenotype 1-1 of Hp

Hp1-1:Hb(III):

Ferric Hp1-1:Hb complex

Hp1-1:Hb(II):

Ferrous Hp1-1:Hb complex

Hp2-2:

Phenotype 2-2 of Hp

Hp2-2:Hb(III):

Ferric Hp2-2:Hb complex

Hp2-2:Hb(II):

Ferrous Hp2-2:Hb complex

NO:

Nitrogen monoxide

SP-like domain:

Serine protease-like domain

References

  1. Kristiansen M, Graversen JH, Jacobsen C, Sonne O, Hoffman HJ, Law K, Moestrup SK (2001) Nature 409:198–201

    Article  CAS  PubMed  Google Scholar 

  2. Buehler PW, Abraham B, Vallelian F, Linnemayr C, Pereira CP, Cipollo JF, Jia Y, Mikolajczyk M, Boretti FS, Schoedon G, Alayash AI, Schaer DJ (2009) Blood 113:2578–2586

    Article  CAS  PubMed  Google Scholar 

  3. Kaempfer T, Duerst E, Gehrig P, Roschitzki B, Rutishauser D, Grossmann J, Schoedon G, Vallelian F, Schaer DJ (2011) J Proteome Res 10:2397–2408

    Article  CAS  PubMed  Google Scholar 

  4. Baek JH, D’Agnillo F, Vallelian F, Pereira CP, Williams MC, Jia Y, Schaer DJ, Buehler PW (2012) J Clin Invest 122:1444–1458

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Alayash AI, Andersen CB, Moestrup SK, Bülow L (2013) Trends Biotechnol 31:2–3

    Article  CAS  PubMed  Google Scholar 

  6. Mollan TL, Jia Y, Banerjee S, Wu G, Kreulen RT, Tsai AL, Olson JS, Crumbliss AL, Alayash AI (2014) Free Radic Biol Med 69:265–277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Andersen CBF, Stødkilde K, Sæderup KL, Kuhlee A, Raunser S, Graversen JH, Moestrup SK (2017) Antioxid Redox Signal 26:814–831

    Article  CAS  PubMed  Google Scholar 

  8. Andersen CB, Torvund-Jensen M, Nielsen MJ, de Oliveira CL, Hersleth HP, Andersen NH, Pedersen JS, Andersen GR, Moestrup SK (2012) Nature 489:456–459

    Article  CAS  PubMed  Google Scholar 

  9. Kurosky A, Barnett DR, Lee TH, Touchstone B, Hay RE, Arnott MS, Bowman BH, Fitch WM (1980) Proc Natl Acad Sci USA 77:3388–3392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wejman JC, Hovsepian D, Wall JS, Hainfeld JF, Greer J (1984) J Mol Biol 174:319–341

    Article  CAS  PubMed  Google Scholar 

  11. Wejman JC, Hovsepian D, Wall JS, Hainfeld JF, Greer J (1984) J Mol Biol 174:343–368

    Article  CAS  PubMed  Google Scholar 

  12. Polticelli F, Bocedi A, Minervini G, Ascenzi P (2008) FEBS J 275:5648–5656

    Article  CAS  PubMed  Google Scholar 

  13. Nagel RL, Gibson QH (1971) J Biol Chem 246:69–73

    CAS  PubMed  Google Scholar 

  14. Stødkilde K, Torvund-Jensen M, Moestrup SK, Andersen CB (2014) Nat Commun 5:5487

    Article  PubMed  CAS  Google Scholar 

  15. Nagel RL, Wittenberg JB, Ranney HM (1965) Biochim Biophys Acta 100:286–289

    Article  CAS  PubMed  Google Scholar 

  16. Nagel RL, Gibson QH (1966) J Mol Biol 22:249–255

    Article  CAS  PubMed  Google Scholar 

  17. Brunori M, Alfsen A, Saggese U, Antonini E, Wyman J (1968) J Biol Chem 243:2950–2954

    CAS  PubMed  Google Scholar 

  18. Gibson QH, Parkhurst LJ, Geraci G (1969) J Biol Chem 244:4668–4676

    CAS  PubMed  Google Scholar 

  19. Alfsen A, Chiancone E, Antonini E, Waks M, Wyman J (1970) Biochim Biophys Acta 207:395–403

    Article  CAS  PubMed  Google Scholar 

  20. Antonini E, Brunori M (1971) Hemoglobin and myoglobin in their reactions with ligands. North Holland Publishing Co, Amsterdam, London

    Google Scholar 

  21. Chiancone E, Antonini E, Brunori M, Alfsen A, Lavialle F (1973) Biochem J 133:205–207

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Perutz MF (1979) Annu Rev Biochem 48:327–386

    Article  CAS  PubMed  Google Scholar 

  23. Azarov I, He X, Jeffers A, Basu S, Ucer B, Hantgan RR, Levy A, Kim-Shapiro DB (2008) Nitric Oxide 18:296–302

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ascenzi P, Coletta M (2018) J Phys Chem B 122:11100–11107

    Article  CAS  PubMed  Google Scholar 

  25. Ascenzi P, De Simone G, Polticelli F, Gioia M, Coletta M (2018) J Biol Inorg Chem 23:437–445

    Article  CAS  PubMed  Google Scholar 

  26. Ascenzi P, Tundo GR, Coletta M (2018) J Inorg Biochem 187:116–122

    Article  CAS  PubMed  Google Scholar 

  27. Ascenzi P, Polticelli F, Coletta M (2019) Sci Rep 9:6780

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. White SL (1975) J Biol Chem 250:1263–1268

    CAS  PubMed  Google Scholar 

  29. Ascenzi P, di Masi A, De Simone G, Gioia M, Coletta M (2019) J Biol Inorg Chem 24:247–255

    Article  CAS  PubMed  Google Scholar 

  30. Ascenzi P, De Simone G, Ciaccio C, Coletta M (2020) J Inorg Biochem 202:110814

    Article  CAS  PubMed  Google Scholar 

  31. Bellelli A, Antonini G, Brunori M, Springer BA, Sligar SG (1990) J Biol Chem 265:18898–18901

    CAS  PubMed  Google Scholar 

  32. Brunori M, Antonini G, Castagnola M, Bellelli A (1992) J Biol Chem 267:2258–2263

    CAS  PubMed  Google Scholar 

  33. Bolognesi M, Bordo D, Rizzi M, Tarricone C, Ascenzi P (1997) Prog Biophys Mol Biol 68:29–68

    Article  CAS  PubMed  Google Scholar 

  34. Milani M, Ouellet Y, Ouellet H, Guertin M, Boffi A, Antonini G, Bocedi A, Mattu M, Bolognesi M, Ascenzi P (2004) Biochemistry 43:5213–5221

    Article  CAS  PubMed  Google Scholar 

  35. Bolli A, Ciaccio C, Coletta M, Nardini M, Bolognesi M, Pesce A, Guertin M, Visca P, Ascenzi P (2008) FEBS J 275:633–645

    Article  CAS  PubMed  Google Scholar 

  36. Ascenzi P, Sbardella D, Santucci R, Coletta M (2016) J Biol Inorg Chem 21:511–522

    Article  CAS  PubMed  Google Scholar 

  37. Barbosa RM, Lopes Jesus AJ, Santos RM, Pereira CL, Marques CF, Rocha BS, Ferreira NR, Ledo A, Laranjin J (2011) Glob J Anal Chem 2:272–284

    CAS  Google Scholar 

  38. Franzini C, Cattozzo G, Besozzi M (1987) J Clin Chem Clin Biochem 25:183–184

    CAS  PubMed  Google Scholar 

  39. Stitt F, Coryell CD (1939) J Am Chem Soc 61:1263–1266

    Article  CAS  Google Scholar 

  40. Cox RP (1977) Biochem J 167:493–495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Bateman H (1910) Proc Camb Phyl Soc 15:423–427

    CAS  Google Scholar 

  42. Lambeth DO, Palmer G (1973) J Biol Chem 248:6095–6103

    CAS  PubMed  Google Scholar 

  43. Olivas E, De Waal DJ, Wilkins RG (1977) J Biol Chem 252:4038–4042

    CAS  PubMed  Google Scholar 

  44. Lister MW, Garvie RC (1959) Can J Chem 37:1567–1574

    Article  CAS  Google Scholar 

  45. Balasubramanian S, Lambright DG, Simmons JH, Gill SJ, Boxer SG (1994) Biochemistry 33:8355–8360

    Article  CAS  PubMed  Google Scholar 

  46. Ascenzi P, Ciaccio C, Coletta M (2007) Biochem Biophys Res Commun 363:931–936

    Article  CAS  PubMed  Google Scholar 

  47. Cox RP, Hollaway MR (1977) Eur J Biochem 74:575–587

    Article  CAS  PubMed  Google Scholar 

  48. Antonini G, Bellelli A, Concetti A, Falcioni G, Brunori M (1994) Biochim Biophys Acta 1025:252–257

    Article  Google Scholar 

  49. Antonini G, Bellelli A, Brunori M, Falcioni G (1996) Biochem J 314:533–540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Boffi A, Ilari A, Spagnuolo C, Chiancone E (1996) Biochemistry 35:8068–8074

    Article  CAS  PubMed  Google Scholar 

  51. Wireko FC, Abraham DJ (1992) Protein Eng 5:3–5

    Article  CAS  PubMed  Google Scholar 

  52. Gray HB, Winkler JR (1996) Annu Rev Biochem 65:537–561

    Article  CAS  PubMed  Google Scholar 

  53. Brunori M, Noble RW, Antonini E, Wyman J (1966) J Biol Chem 241:5238–5243

    CAS  PubMed  Google Scholar 

  54. Unzai S, Eich R, Shibayama N, Olson JS, Morimoto H (1998) J Biol Chem 273:23150–23159

    Article  CAS  PubMed  Google Scholar 

  55. Gibson QH (1973) Proc Natl Acad Sci USA 70:1–4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Sharma VS, Vedvick TS, Magde D, Luth R, Friedman D, Schmidt MR, Ranney HM (1980) J Biol Chem 256:5879–5884

    Google Scholar 

  57. Lane-Serff H, MacGregor P, Peacock L, Macleod OJ, Kay C, Gibson W, Higgins MK, Carrington M (2016) Elife 5:e13044

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Park SY, Yokoyama T, Shibayama N, Shiro Y, Tame JR (2006) J Mol Biol 360:690–701

    Article  CAS  PubMed  Google Scholar 

  59. Vandegriff KD, Le Tellier YC, Winslow RM, Rohlfs RJ, Olson JS (1991) J Biol Chem 266:17049–17059

    CAS  PubMed  Google Scholar 

  60. Savino C, Miele AE, Draghi F, Johnson KA, Sciara G, Brunori M, Vallone B (2009) Biopolymers 91:1097–1107

    Article  CAS  PubMed  Google Scholar 

  61. Birukou I, Maillett DH, Birukova A, Olson JS (2011) Biochemistry 50:7361–7374

    Article  CAS  PubMed  Google Scholar 

  62. Jones EM, Monza E, Balakrishnan G, Blouin GC, Mak PJ, Zhu Q, Kincaid JR, Guallar V, Spiro TG (2014) J Am Chem Soc 136:10325–10339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Sawicki CA, Gibson QH (1977) J Biol Chem 252:7538–7547

    CAS  PubMed  Google Scholar 

  64. Hydrogen cyanide, PubChem CID: 768

  65. Perrella M, Davids N, Rossi-Bernardi L (1992) J Biol Chem 267:8744–8751

    CAS  PubMed  Google Scholar 

  66. Kawamura K, Kagiyama S, Ogawa A, Yanase T (1972) Biochim Biophys Acta 285:22–27

    Article  CAS  PubMed  Google Scholar 

  67. Nakagawa A, Lui FE, Wassaf D, Yefidoff-Freedman R, Casalena D, Palmer MA, Meadows J, Mozzarelli A, Ronda L, Abdulmalik O, Bloch KD, Safo MK, Zapol WM (2014) ACS Chem Biol 9:2318–2325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) J Comput Chem 25:1605–1612

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the grant of Dipartimenti di Eccellenza, MIUR (Legge 232/2016, Articolo 1, Comma 314-337; to P.A.).

Author information

Author notes

  1. Paolo Ascenzi and Giovanna De Simone have contributed equally to this paper.

Authors and Affiliations

  1. Interdepartmental Laboratory for Electron Microscopy, Roma Tre University, Via della Vasca Navale 79, 00146, Rome, Italy

    Paolo Ascenzi

  2. Department of Sciences, Roma Tre University, Viale Guglielmo Marconi 446, 00146, Rome, Italy

    Giovanna De Simone

  3. Department of Clinical Sciences and Translational Medicine, University of Roma “Tor Vergata”, Via Montpellier 1, 00133, Rome, Italy

    Grazia R. Tundo & Massimo Coletta

Authors
  1. Paolo Ascenzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Giovanna De Simone
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Grazia R. Tundo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Massimo Coletta
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paolo Ascenzi.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ascenzi, P., De Simone, G., Tundo, G.R. et al. Kinetics of cyanide and carbon monoxide dissociation from ferrous human haptoglobin:hemoglobin(II) complexes. J Biol Inorg Chem 25, 351–360 (2020). https://doi.org/10.1007/s00775-020-01766-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00775-020-01766-3

Keywords

Search

Navigation