Studies on the Oxygen Activation Mechanisms by Heme Enzymes: Usage of Hemoprotein Mutants and Synthetic Heme Models

Yoshihito Watanabe, Toshitaka Matsui

Research output: Contribution to journalArticle

Abstract

In order to understand roles of amino acid residues around heme vicinity in the oxygen activation by cytochrome P-450 and peroxidases, we have employed two strategies. One was the usage of synthetic heme models and the other was mutation of key residues in hemoproteins. Through the model studies, we have characterized all conceivable intermediates postulated in enzymic systems. In addition, push -pull effect on the oxygen activation was experimentally demonstrated. On the other hand, mutant myoglobins having cysteine as the proximal ligand were prepared to understand roles of thiolate ligand in the oxygen activation by cytochrome P-450. Further, hydrogen bonding between Asn and distal His in peroxidases has been shown to be important to control both the oxygen activation and the substrate oxidation. On the basis of these enzymic and model studies, we have synthesized artificial peroxide-dependent heme enzymes by site-directed double point mutation of sperm whale myoglobin. The resulting Mb mutants exhibit remarkable oxidation activities with high enantioselectivities in sulfoxidation and epoxidation.

Original languageEnglish
Pages (from-to)37-46
Number of pages10
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume54
Issue number12
Publication statusPublished - 1996 Dec 1
Externally publishedYes

Keywords

  • Cytochrome P-450
  • Enantioselectivity
  • Heme
  • Hemoprotein
  • Mutation
  • Myoglobin
  • Oxygen activation
  • Peroxidase
  • Push-pull effect

ASJC Scopus subject areas

  • Organic Chemistry

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