Computational exploration of the catalytic mechanism of dopamine β-monooxygenase: Modeling of its mononuclear copper active sites

Takashi Kamachi, Naoki Kihara, Yoshihito Shiota, Kazunari Yoshizawa

研究成果: Contribution to journalArticle査読

69 被引用数 (Scopus)

抄録

Dopamine hydroxylation by the copper-superoxo, -hydroperoxo, and -oxo species of dopamine β-monooxygenase (DBM) is investigated using theoretical calculations to identify the active species in its reaction and to reveal the key functions of the surrounding amino acid residues in substrate binding. A 3D model of rat DBM is constructed by homology modeling using the crystal structure of peptidylglycine α-hydroxylating monooxygenase (PHM) with a high sequence identity of 30% as a template. In the constructed 3D model, the CuA site in domain 1 is coordinated by three histidine residues, His265, His266, and His336, while the CuB site in domain 2 is coordinated by two histidine residues, His415 and His417, and by a methionine residue, Met490. The three Glu268, Glu369, and Tyr494 residues are suggested to play an important role in the substrate binding at the active site of DBM to enable the stereospecific hydrogen-atom abstraction. Quantum mechanical/molecular mechanical (QM/MM) calculations are performed to determine the structure of the copper-superoxo, -hydroperoxo, and -oxo species in the whole-enzyme model with about 4700 atoms. The reactivity of the three oxidants is evaluated in terms of density-functional-theory calculations with small models extracted from the QM region of the whole-enzyme model.

本文言語英語
ページ(範囲)4226-4236
ページ数11
ジャーナルInorganic Chemistry
44
12
DOI
出版ステータス出版済み - 6 13 2005

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry

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