Histidine Residues Involved in Heme Binding by Prostaglandin Endoperoxide Synthase

  • T. Shimokawa
  • W. L. Smith
Part of the Developments in Oncology book series (DION, volume 71)

Abstract

Heme is required for the expression of both the peroxidase and cyclooxygenase activities of PGH synthase (1). There are spectral data indicating that the heme moiety of PGH synthase is liganded via two imidazole groups (2, 3). Since heme is required for both cyclooxygenase and peroxidase activities, replacement of a required heme ligand should cause the coordinate loss of both activities. There are thirteen conserved histidine residues in PGH synthase (4). We replaced each of these histidines with glutamine residues and compared the cyclooxygenase and hydroperoxidase activities of the native and mutant PGH synthases (4); in those instances in which the Gin mutant was inactive, we performed a second replacement with a smaller alanine group and again measured enzyme activity. The results seen with the glutamine and alanine mutations were qualitatively the same.

Keywords

Propionate Carboxylate Glutamine Trypsin Prostaglandin 

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References

  1. 1.
    Ogino, N., Ohki, S., Yamamoto, S., and Hayaishi, O. J. Biol. Chem. 253: 5061–5065, 1978.PubMedGoogle Scholar
  2. 2.
    Kulmacz, R.J., Tsai, A-L. and Palmer, G. J. Biol. Chem. 262:10524–10531, 1987.PubMedGoogle Scholar
  3. 3.
    Lambeir, A.M., Markey, CM., Dunford, H.B. and Marnett, L.J. J. Biol. Chem. 260: 14894–14896, 1985.PubMedGoogle Scholar
  4. 4.
    Shimokawa, T. and Smith, W.L. J. Biol. Chem. 266: 6168–6173, 1991.PubMedGoogle Scholar
  5. 5.
    Shimokawa, T., Kulmacz, R.J., DeWitt, D.L. and Smith, W.L. J. Biol. Chem. 265:1–2, 1990.Google Scholar
  6. 6.
    Kunkel, T.A., Roberts, J.D. and Zakour, R.A. Methods Enzymol. 154: 367–382, 1987.PubMedCrossRefGoogle Scholar
  7. 7.
    Marnett, L.J., Chen, Y-N.P., Maddipati, K.R., Ple, P. and Labeque, R. J. Biol. Chem. 263: 16532–16535, 1988.PubMedGoogle Scholar
  8. 8.
    DeWitt, D.L., El-Harith, E.A., Kraemer, S.A., Andrews, M.J., Yao, E.F., Armstrong, R.L and Smith, W.L. J. Biol. Chem. 265: 5192–5198, 1990.PubMedGoogle Scholar
  9. 9.
    Kimura, S. and lkeda-Saito, M. Proteins: Struc. Func. Gene. 3:113–120, 1988.CrossRefGoogle Scholar
  10. 10.
    Edwards, S.L. and Poulos, T.L. J. Biol. Chem. 265: 2588–2595, 1990.PubMedGoogle Scholar
  11. 11.
    Dietz, R., Nastainczyk, W. and Ruf, H.H. Eur. J. Biochem. 171: 321–328, 1988.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • T. Shimokawa
    • 1
  • W. L. Smith
    • 1
  1. 1.Department of BiochemistryMichigan State UniversityEast LansingUSA

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