Amino Acids Essential to Catalysis by Prostaglandin Endoperoxide Synthase

  • Teruhiko Shimokawa
  • William L. Smith
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


The recent availability of cDNAs containing the entire coding region of prostaglandin endoperoxide (PGH) synthase (1–3) and the development of constructs which can be used for expressing the enzyme in vitro (4–6) permits the use of site-directed mutagenesis to characterize this enzyme (4–7). It is now possible to compare properties of mutagenized PGH synthases to the native enzyme in order to determine the effects of modifying any amino acid on the cyclooxygenase and/or hydroperoxidase activities, the size and spectral properties of the protein, and subtle changes in kinetic constants. Accordingly, we have applied mutagenesis procedures to identify amino acids which are important in cyclooxygenase and hydroperoxidase catalysis, heme binding, and the interaction of PGH synthase with nonsteroidal anti-inflammatory drugs. Here we present a summary of these studies in the context of developing a model for the cyclooxygenase and peroxidase active sites of the enzyme.


Heme Binding Cyclooxygenase Activity Prostaglandin Endoperoxide Tyrosyl Radical Trypsin Cleavage 
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Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Teruhiko Shimokawa
    • 1
  • William L. Smith
    • 1
  1. 1.Department of BiochemistryMichigan State UniversityEast LansingUSA

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