Enhancement of enzymatic activity for myoglobins by modification of heme-propionate side chains

Takashi Hayashi, Hideaki Sato, Takashi Matsuo, Takaaki Matsuda, Yutaka Hitomi, Yoshio Hisaeda

    研究成果: ジャーナルへの寄稿簡易調査査読

    9 被引用数 (Scopus)

    抄録

    The modification of myoglobin is an attractive process not only for understanding its molecular mechanism but also for engineering the protein function. The strategy of myoglobin functionalization can be divided into at least two approaches: site-directed mutagenesis and reconstitution with a non-natural prosthetic group. The former method enables us to mainly modulate the physiological function, while the latter has the advantage of introducing a new function on the protein. Particularly, replacement of the native hemin with an artificially created hemin having hydrophobic moieties at the terminal of the heme-propionate side chains serves as an appropriate substrate-binding site near the heme pocket, and consequently enhances the peroxidase and peroxygenase activities for the reconstituted myoglobin. In addition, the incorporation of the synthetic hemin bearing modified heme-propionates into an appropriate apomyoglobin mutant drastically enhances the peroxidase activity. In contrast, to convert myoglobin into a cytochrome P450 enzyme, a flavin moiety as an electron transfer mediator was introduced at the terminal of the heme-propionate side chain. The flavomyoglobin catalyzes the deformylation of 2-phenylpropanal in the presence of NADH under aerobic conditions through the peroxoanion formation from the oxygenated species. In addition, modification of the heme-propionate side chains has an significant influence on regulating the reactivity of the horseradish peroxidase. Furthermore, the heme-propionate side chain can form a metal binding site with a carboxylate residue in the heme pocket. These studies indicate that modification of the heme-propionate side chains can be a new and effective way to engineer functions for the hemoproteins.

    本文言語英語
    ページ(範囲)255-264
    ページ数10
    ジャーナルJournal of Porphyrins and Phthalocyanines
    8
    1-3
    DOI
    出版ステータス出版済み - 2004

    !!!All Science Journal Classification (ASJC) codes

    • 化学 (全般)

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