Skip to main content

Advertisement

SpringerLink
Log in

Self-hydroxylation of taurine/α-ketoglutarate dioxygenase: evidence for more than one oxygen activation mechanism

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

Abstract

2-Aminoethanesulfonic acid (taurine)/α-ketoglutarate (αKG) dioxygenase (TauD) is a mononuclear non-heme iron enzyme that catalyzes the hydroxylation of taurine to generate sulfite and aminoacetaldehyde in the presence of O2, αKG, and Fe(II). Fe(II)TauD complexed with αKG or succinate, the decarboxylated product of αKG, reacts with O2 in the absence of prime substrate to generate 550- and 720-nm chromophores, respectively, that are interconvertible by the addition or removal of bound bicarbonate and have resonance Raman features characteristic of an Fe(III)–catecholate complex. Mutagenesis studies suggest that both reactions result in the self-hydroxylation of the active-site residue Tyr73, and liquid chromatography nano-spray mass spectrometry/mass spectrometry evidence corroborates this result for the succinate reaction. Furthermore, isotope-labeling resonance Raman studies demonstrate that the oxygen atom incorporated into the tyrosyl residue derives from H2 18O and 18O2 for the αKG and succinate reactions, respectively, suggesting distinct mechanistic pathways. Whereas the αKG-dependent hydroxylation likely proceeds via an Fe(IV)=O intermediate that is known to be generated during substrate hydroxylation, we propose Fe(III)–OOH (or Fe(V)=O) as the oxygenating species in the succinate-dependent reaction. These results demonstrate the two oxygenating mechanisms available to enzymes with a 2-His-1-carboxylate triad, depending on whether the electron source donates one or two electrons.

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
Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Abbreviations

αKG:

α-Ketoglutarate

DOPA:

Dihydroxyphenylalanine

HPPD:

4-Hydroxyphenylpyruvate dioxygenase

HppE:

(S)-2-Hydroxypropylphosphonic acid epoxidase

LC/MS/MS:

Liquid chromatography nano-spray mass spectrometry/mass spectrometry

PheH:

Phenylalanine hydroxylase

PMI:

Phosphomannose isomerase

RNR R2:

R2 subunit of ribonucleotide reductase

TauD:

Taurine/αKG dioxygenase

TfdA:

2,4-Dichlorophenoxyacetate/αKG dioxygenase

Tris:

Tris(hydroxymethyl)aminomethane

TyrH:

Tyrosine hydroxylase

References

  1. Solomon EI, Brunold TC, Davis MI, Kemsley JN, Lee S-K, Lehnert N, Neese F, Skulan AJ, Yang Y-S, Zhou J (2000) Chem Rev 100:235–349

    Article  PubMed  CAS  Google Scholar 

  2. Costas M, Mehn MP, Jensen MP, Que L Jr (2004) Chem Rev 104:939–986

    Article  PubMed  CAS  Google Scholar 

  3. Koehntop KD, Emerson JP, Que L Jr (2005) J Biol Inorg Chem 10:87–93

    Article  PubMed  CAS  Google Scholar 

  4. Hegg EL, Que L Jr (1997) Eur J Biochem 250:625–629

    Article  PubMed  CAS  Google Scholar 

  5. Que L Jr (2000) Nat Struct Biol 7:182–184

    Article  PubMed  CAS  Google Scholar 

  6. Hausinger RP (2004) Crit Rev Biochem Mol Biol 39:21–68

    Article  PubMed  CAS  Google Scholar 

  7. Trewick SC, Henshaw TF, Hausinger RP, Lindahl T, Sedgwick B (2002) Nature 419:174–178

    Article  PubMed  CAS  Google Scholar 

  8. Aas PA, Otterlei M, Falnes PØ, Vågbø CB, Skorpen F, Akbari M, Sundheim O, Bjørås M, Slupphaug G, Seeberg E, Krokan HE (2003) Nature 421:859–863

    Article  PubMed  CAS  Google Scholar 

  9. Ivan M, Kondo K, Yang H, Kim W, Valiando J, Ohh M, Salic A, Asara JM, Lane WS, Kaelin WG Jr (2001) Science 292:464–468

    Article  PubMed  CAS  Google Scholar 

  10. Jaakkola P, Mole DR, Tian Y-M, Wilson MI, Gielbert J, Gaskell SJ, von Kriegsheim A, Hebestreit HF, Mukherji M, Schofield CJ, Maxwell PH, Pugh CW, Ratcliffe PJ (2001) Science 292:468–472

    Article  PubMed  CAS  Google Scholar 

  11. Dann CE III, Bruick RK, Deisenhofer J (2002) Proc Natl Acad Sci USA 99:15351–15356

    Article  PubMed  CAS  Google Scholar 

  12. Fukumori F, Hausinger RP (1993) J Biol Chem 268:24311–24317

    PubMed  CAS  Google Scholar 

  13. Zhang Z, Ren J, Stammers DK, Baldwin JE, Harlos K, Schofield CJ (2000) Nat Struct Biol 7:127–133

    Article  PubMed  CAS  Google Scholar 

  14. Clifton IJ, Hsueh L-C, Baldwin JE, Harlos K, Schofield CJ (2001) Eur J Biochem 268:6625–6636

    Article  PubMed  CAS  Google Scholar 

  15. Lukaĉin R, Gröning I, Pieper U, Matern U (2000) Eur J Biochem 267:853–860

    Article  PubMed  Google Scholar 

  16. Eichhorn E, van der Ploeg JR, Kertesz MA, Leisinger T (1997) J Biol Chem 272:23031–23036

    Article  PubMed  CAS  Google Scholar 

  17. Elkins JM, Ryle MJ, Clifton IJ, Hotopp JCD, Lloyd JS, Burzlaff NI, Baldwin JE, Hausinger RP, Roach PL (2002) Biochemistry 41:5185–5192

    Article  PubMed  CAS  Google Scholar 

  18. Valegård K, van Scheltinga ACT, Lloyd MD, Hara T, Ramaswamy S, Perrakis A, Thompson A, Lee H-J, Baldwin JE, Schofield CJ, Hajdu J, Andersson I (1998) Nature 394:805–809

    Article  PubMed  Google Scholar 

  19. Ryle MJ, Padmakumar R, Hausinger RP (1999) Biochemistry 38:15278–15286

    Article  PubMed  CAS  Google Scholar 

  20. Ho RYN, Mehn MP, Hegg EL, Liu A, Ryle MJ, Hausinger RP, Que L Jr (2001) J Am Chem Soc 123:5022–5029

    Article  PubMed  CAS  Google Scholar 

  21. Price JC, Barr EW, Tirupati B, Bollinger JM Jr, Krebs C (2003) Biochemistry 42:7497–7508

    Article  PubMed  CAS  Google Scholar 

  22. Price JC, Barr EW, Glass TE, Krebs C, Bollinger JM Jr (2003) J Am Chem Soc 125:13008–13009

    Article  PubMed  CAS  Google Scholar 

  23. Proshlyakov DA, Henshaw TF, Monterosso GR, Ryle MJ, Hausinger RP (2004) J Am Chem Soc 126:1022–1023

    Article  PubMed  CAS  Google Scholar 

  24. Riggs-Gelasco PJ, Price JC, Guyer RB, Brehm JH, Barr EW, Bollinger JM Jr, Krebs C (2004) J Am Chem Soc 126:8108–8109

    Article  PubMed  CAS  Google Scholar 

  25. Grzyska PK, Ryle MJ, Monterosso GR, Liu J, Ballou DP, Hausinger RP (2005) Biochemistry 44:3845–3855

    Article  PubMed  CAS  Google Scholar 

  26. Price JC, Barr EW, Hoffart LM, Krebs C, Bollinger JM Jr (2005) Biochemistry 44:8138–8147

    Article  PubMed  CAS  Google Scholar 

  27. Ryle MJ, Liu A, Muthukumaran RB, Ho RYN, Koehntop KD, McCracken J, Que L Jr, Hausinger RP (2003) Biochemistry 42:1854–1862

    Article  PubMed  CAS  Google Scholar 

  28. Ryle MJ, Koehntop KD, Liu A, Que L Jr, Hausinger RP (2003) Proc Natl Acad Sci USA 100:3790–3795

    Article  PubMed  CAS  Google Scholar 

  29. Lord RC, Yu N-t (1970) J Mol Biol 50:509–524

    Article  PubMed  CAS  Google Scholar 

  30. Hernandez VP, Higgins L, Fallon AM (2003) Dev Comp Immunol 27:11–20

    Article  PubMed  CAS  Google Scholar 

  31. Liu P, Mehn MP, Yan F, Zhao Z, Que L Jr, Liu H-w (2004) J Am Chem Soc 126:10306–10312

    Article  PubMed  CAS  Google Scholar 

  32. Ling J, Sahlin M, Sjöberg B-M, Loehr TM, Sanders-Loehr J (1994) J Biol Chem 269:5595–5601

    PubMed  CAS  Google Scholar 

  33. Smith JJ, Thomson AJ, Proudfoot AE, Wells TN (1997) Eur J Biochem 244:325–333

    Article  PubMed  CAS  Google Scholar 

  34. Andersson KK, Cox DD, Que L Jr, Flatmark T, Haavik J (1988) J Biol Chem 263:18621–18626

    PubMed  CAS  Google Scholar 

  35. Andersson KK, Vassort C, Brennan BA, Que L Jr, Haavik J, Flatmark T, Gros F, Thibault J (1992) Biochem J 284:687–695

    PubMed  CAS  Google Scholar 

  36. Michaud-Soret I, Andersson KK, Que L Jr, Haavik J (1995) Biochemistry 34:5504–5510

    Article  PubMed  CAS  Google Scholar 

  37. Salama S, Stong JD, Neilands JB, Spiro TG (1978) Biochemistry 17:3781–3785

    Article  PubMed  CAS  Google Scholar 

  38. Pyrz JW, Roe AL, Stern LJ, Que L Jr (1985) J Am Chem Soc 107:614–620

    Article  CAS  Google Scholar 

  39. Baldwin J, Voegtli WC, Khidekel N, Moënne-Loccoz P, Krebs C, Pereira AS, Ley BA, Huynh BH, Loehr TM, Riggs-Gelasco PJ, Rosenzweig AC, Bollinger JM Jr (2001) J Am Chem Soc 123:7017–7030

    Article  PubMed  CAS  Google Scholar 

  40. Bradley FC, Lindstedt S, Lipscomb JD, Que L Jr, Roe AL, Rundgren M (1986) J Biol Chem 261:11693–11696

    PubMed  CAS  Google Scholar 

  41. Liu A, Ho RYN, Que L Jr, Ryle MJ, Phinney BS, Hausinger RP (2001) J Am Chem Soc 123:5126–5127

    Article  PubMed  CAS  Google Scholar 

  42. Cox DD, Benkovic SJ, Bloom LM, Bradley FC, Nelson MJ, Que L Jr, Wallick DE (1988) J Am Chem Soc 110:2026–2032

    Article  CAS  Google Scholar 

  43. Sabourin PJ, Bieber LL (1982) J Biol Chem 257:7468–7471

    PubMed  CAS  Google Scholar 

  44. Baldwin JE, Adlington RM, Crouch NP, Schofield CJ, Turner NJ, Aplin RT (1991) Tetrahedron 47:9881–9900

    Article  CAS  Google Scholar 

  45. van der Ploeg JR, Weiss MA, Saller E, Nashimoto H, Saito N, Kertesz MA, Leisinger T (1996) J Bacteriol 178:5438–5446

    PubMed  Google Scholar 

  46. Bollinger JM Jr, Edmondson DE, Huynh BH, Filley J, Norton JR, Stubbe J (1991) Science 253:292–298

    Article  PubMed  CAS  Google Scholar 

  47. Gibson DT, Parales RE (2000) Curr Opin Biotechnol 11:236–243

    Article  PubMed  CAS  Google Scholar 

  48. Ormö M, deMaré F, Regnström K, Åberg A, Sahlin M, Ling J, Loehr TM, Sanders-Loehr J, Sjöberg B-M (1992) J Biol Chem 267:8711–8714

    PubMed  Google Scholar 

  49. Logan DT, deMaré F, Persson BO, Slaby A, Sjöberg B-M, Nordlund P (1998) Biochemistry 37:10798–10807

    Article  PubMed  CAS  Google Scholar 

  50. Goodwill KE, Sabatier C, Stevens RC (1998) Biochemistry 37:13437–13445

    Article  PubMed  CAS  Google Scholar 

  51. Åberg A, Ormö M, Nordlund P, Sjöberg B-M (1993) Biochemistry 32:9845–9850

    Article  PubMed  Google Scholar 

  52. Kinzie SD, Thevis M, Ngo K, Whitelegge J, Loo JA, Abu-Omar MM (2003) J Am Chem Soc 125:4710–4711

    Article  PubMed  CAS  Google Scholar 

  53. Henshaw TF, Feig M, Hausinger RP (2004) J Inorg Biochem 98:856–861

    Article  PubMed  CAS  Google Scholar 

  54. Parkin SE, Chen S, Ley BA, Mangravite L, Edmondson DE, Huynh BH, Bollinger JM Jr (1998) Biochemistry 37:1124–1130

    Article  PubMed  CAS  Google Scholar 

  55. Kolberg M, Logan DT, Bleifuss G, Pötsch S, Sjöberg B-M, Gräslund A, Lubitz W, Lassmann G, Lendzian F (2005) J Biol Chem 280:11233–11246

    Article  PubMed  CAS  Google Scholar 

  56. Ormö M, Regnström K, Wang Z, Que L Jr, Sahlin M, Sjöberg B-M (1995) J Biol Chem 270:6570–6576

    Article  PubMed  Google Scholar 

  57. Lindstedt S, Rundgren M (1982) J Biol Chem 257:11922–11931

    PubMed  CAS  Google Scholar 

  58. Ellis HR, Daubner SC, McCulloch RI, Fitzpatrick PF (1999) Biochemistry 38:10909–10914

    Article  PubMed  CAS  Google Scholar 

  59. Müller I, Stückl C, Wakeley J, Kertesz M, Usón I (2005) J Biol Chem 280:5716–5723

    Article  PubMed  CAS  Google Scholar 

  60. Zhang Z, Barlow JN, Baldwin JE, Schofield CJ (1997) Biochemistry 36:15999–16007

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the National Institutes of Health, GM33162 (to L.Q.) and GM063584 (to R.P.H.), a Chemistry Biology Interface Traineeship to K.D.K. (GM08700), and a postdoctoral fellowship to M.J.R (GM20196). We thank Piotr K. Grzyska for providing purified TauD for some of these studies.

Author information

Author notes

  1. Kevin D. Koehntop

    Present address: The Scripps Research Institute, La Jolla, CA, 92037, USA

  2. Matthew J. Ryle

    Present address: Idexx Laboratories, Westbrook, ME, 04092, USA

Authors and Affiliations

  1. Department of Chemistry and Center for Metals in Biocatalysis, University of Minnesota, Minneapolis, MN, 55455, USA

    Kevin D. Koehntop & Lawrence Que Jr

  2. Department of Microbiology and Molecular Genetics and Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, 48824, USA

    Matthew J. Ryle & Robert P. Hausinger

  3. Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, 55455, USA

    Sudha Marimanikkuppam

Authors
  1. Kevin D. Koehntop
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sudha Marimanikkuppam
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Matthew J. Ryle
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert P. Hausinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lawrence Que Jr
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lawrence Que Jr.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koehntop, K.D., Marimanikkuppam, S., Ryle, M.J. et al. Self-hydroxylation of taurine/α-ketoglutarate dioxygenase: evidence for more than one oxygen activation mechanism. J Biol Inorg Chem 11, 63–72 (2006). https://doi.org/10.1007/s00775-005-0059-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00775-005-0059-4

Keywords

Search

Navigation