Advertisement

Journal of Molecular Modeling

, Volume 16, Issue 11, pp 1673–1677 | Cite as

On the observation of a gem diol intermediate after O–O bond cleavage by extradiol dioxygenases. A hybrid DFT study

  • Tomasz Borowski
  • Valentin Georgiev
  • Per E. M. Siegbahn
Original Paper

Abstract

Catalytic cycle intermediates of a representative extradiol dioxygenase, homoprotocatechuate 2,3-dioxygenase (HPCD), have recently been characterized in crystallo by Kovaleva and Lipscomb. The structures of the identified species indicate that the process of inserting oxygen into the catechol ring occurs stepwise, and involves an Fe(II)-alkylperoxo intermediate and its O–O cleavage product: a gem diol species. In general, these findings corroborate the results of our previous computational studies; however, the fact that the gem diol species is stable enough to be observed in the crystal form seems to be at odds with the computational mechanistic data, which suggest that this intermediate should very readily and spontaneously convert to the epoxide species. The key question then becomes what is actually observed in the X-ray experiments. Here we report additional computational studies undertaken with the hope of clarifying this issue. The results obtained for active site models hosting both the native and the alternative (4-sulfonylcatechol) substrate indicate that the stability of the gem diol species is substantially increased if an electron and a proton are added. If this occurs somehow, the lifetime of the intermediate should be sufficient to observe it.

Keywords

Homoprotocatechuate 2,3-dioxygenase Extradiol Ring cleavage Density functional calculations 

Notes

Acknowledgments

We are grateful to Sven de Marothy for providing us with his XYZ-Viewer program, which was used to produce Fig. 3. T.B. acknowledges support from the Polish State Committee for Scientific Research (Grant N301 093036).

Supplementary material

894_2010_652_MOESM1_ESM.pdf (114 kb)
(PDF 114 kb)

References

  1. 1.
    Siegbahn PEM, Haeffner F (2004) Mechanism for catechol ring-cleavage by non-heme iron extradiol dioxygenases. J Am Chem Soc 126:8919–8932CrossRefGoogle Scholar
  2. 2.
    Georgiev V, Borowski T, Siegbahn PEM (2006) Theoretical study of the catalytic reaction mechanism of MndD. J Biol Inorg Chem 11:571–585CrossRefGoogle Scholar
  3. 3.
    Georgiev V, Borowski T, Blomberg MR, Siegbahn PEM (2008) A comparison of the reaction mechanisms of iron- and manganese-containing 2,3-HPCD: an important spin transition for manganese. J Biol Inorg Chem 13:929–940Google Scholar
  4. 4.
    Borowski T, Georgiev V, Siegbahn PEM (2005) Catalytic reaction mechanism of homogentisate dioxygenase: a hybrid DFT study. J Am Chem Soc 127:17303–17314CrossRefGoogle Scholar
  5. 5.
    Kovaleva EG, Lipscomb JD (2007) Crystal structures of Fe2+ dioxygenase superoxo, alkylperoxo, and bound product intermediates. Science 316:453–457Google Scholar
  6. 6.
    Kovaleva EG, Lipscomb JD (2008) Intermediate in the O–O bond cleavage reaction of an extradiol dioxygenase. Biochemistry 47:11168–11170Google Scholar
  7. 7.
    Becke ADJ (1993) Density-functional thermochemistry. III. The role of exact exchange. Chem Phys 98:5648–5652Google Scholar
  8. 8.
    Lee C, Yang W, Parr RG (1988) Development of the Colle–Salvetti correlation energy formula into a functional of the electron density. Phys Rev B37:785–789Google Scholar
  9. 9.
    Schrödinger, Inc. (2007) Jaguar 7. Schrödinger, Inc., PortlandGoogle Scholar
  10. 10.
    Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Montgomery JA Jr, Vreven T, Kudin KN, Burant JC, Millam JM, Iyengar SS, Tomasi J, Barone V, Mennucci B, Cossi M, Scalmani G, Rega N, Petersson GA, Nakatsuji H, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Klene M, Li X, Knox JE, Hratchian HP, Cross JB, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Ayala PY, Morokuma K, Voth GA, Salvador P, Dannenberg JJ, Zakrzewski VG, Dapprich S, Daniels AD, Strain MC, Farkas O, Malick DK, Rabuck AD, Raghavachari K, Foresman JB, Ortiz JV, Cui Q, Baboul AG, Clifford S, Cioslowski J, Stefanov BB, Liu G, Liashenko A, Piskorz P, Komaromi I, Martin RL, Fox DJ, Keith T, Al-Laham MA, Peng CY, Nanayakkara A, Challacombe M, Gill PMW, Johnson B, Chen W, Wong MW, Gonzalez C, Pople JA (2003) Gaussian 03, Revision E.01. Gaussian Inc., PittsburghGoogle Scholar
  11. 11.
    Curtiss L, Raghavachari K, Redfern P, Pople J (1997) Assessment of Gaussian-2 and density functional theories for computation of enthalpies of formation. J Chem Phys 106:1063–1079Google Scholar
  12. 12.
    Tannor DJ, Marten B, Murphy R, Friesner RA, Sitkoff D, Nicholls A, Ringnalda M, Goddard WA III, Honig B (1994) Accurate first principles calculation of molecular charge distributions and solvation energies from ab initio quantum mechanics and continuum dielectric theory. J Am Chem Soc 116:11875–11882CrossRefGoogle Scholar
  13. 13.
    Marten B, Kim K, Cortis C, Friesner RA, Murphy R, Ringnalda M, Sitkoff D, Honig B (1996) New model for calculation of solvation free energies: correction of self-consistent reaction field continuum dielelectric theory for short-range hydrogen-bonding effects. J Phys Chem 100:11775–11788CrossRefGoogle Scholar
  14. 14.
    Yano J, Kern J, Irrgang K-D, Latimer MJ, Bergmann U, Glatzel P, Pushkar Y, Biesiadka J, Loll B, Sauer K, Messinger J, Zouni A, Yachandra VK (2005) X-ray damage to the Mn4 Ca complex in single crystals of photosystem II: a case study for metalloprotein crystallography. Proc Natl Acad Sci USA 102:12047–12052CrossRefGoogle Scholar
  15. 15.
    Yamahara R, Ogo S, Masuda H, Watanabe Y (2002) (Catecholato)iron(III) complexes: structural and functional models for the catechol-bound iron(III) form of catechol dioxygenases. J Inorg Biochem 88:284–294CrossRefGoogle Scholar
  16. 16.
    Tsodikov OV, Record MT Jr, Sergeev YV (2002) A novel computer program for fast exact calculation of accessible and molecular surface areas and average surface curvature. J Comput Chem 23:600–609CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Tomasz Borowski
    • 1
  • Valentin Georgiev
    • 2
  • Per E. M. Siegbahn
    • 2
  1. 1.Institute of Catalysis and Surface Chemistry, Polish Academy of SciencesCracowPoland
  2. 2.Department of Physics, Stockholm Center for Physics, Astronomy and BiotechnologyStockholm UniversityStockholmSweden

Personalised recommendations