A new understanding on how heme metabolism occurs in heme oxygenase

Water-assisted oxo mechanism

Takashi Kamachi, Tomonori Nishimi, Kazunari Yoshizawa

研究成果: ジャーナルへの寄稿記事

3 引用 (Scopus)

抄録

Heme metabolism by heme oxygenase (HO) is investigated with quantum mechanical/molecular mechanical (QM/MM) calculations. A mechanism assisted by water is proposed: (1) an iron-oxo species and a water molecule are generated by the heterolytic cleavage of the O-O bond of an iron-hydroperoxo species in a similar way to P450-mediated reactions, (2) a hydrogen atom abstraction by the iron-oxo species from the generated water molecule and the C-O bond formation between the water molecule and the α-meso carbon take place simultaneously. The water molecule is hydrogen-bonded to the oxo ligand and to the water cluster in the active site of HO. The water cluster can control the position of the generated water molecule to ensure the regioselective oxidation of heme at the α-meso position, at the same time, can facilitate the oxidation by stabilizing a positive charge on the water molecule in the transition state. A key difference between HO and P450 is observed in the structure of the active site; Thr252 in P450 blocks the access of the water molecule to the α-meso position, and can thus suppress the undesired heme oxidation for P450.

元の言語英語
ページ(範囲)11642-11650
ページ数9
ジャーナルDalton Transactions
41
発行部数38
DOI
出版物ステータス出版済み - 10 14 2012

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Heme Oxygenase (Decyclizing)
Heme
Metabolism
Water
Molecules
Iron
Oxidation
Hydrogen
Carbon
Ligands

All Science Journal Classification (ASJC) codes

  • Inorganic Chemistry

これを引用

A new understanding on how heme metabolism occurs in heme oxygenase : Water-assisted oxo mechanism. / Kamachi, Takashi; Nishimi, Tomonori; Yoshizawa, Kazunari.

:: Dalton Transactions, 巻 41, 番号 38, 14.10.2012, p. 11642-11650.

研究成果: ジャーナルへの寄稿記事

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