Quantum Chemical Approach to the Mechanism for the Biological Conversion of Tyrosine to Dopaquinone
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- Toshinori Inoue
- Institute for Materials Chemistry and Engineering, Kyushu University, Nishi-ku, Fukuoka 819-0395, Japan
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- Yoshihito Shiota
- Institute for Materials Chemistry and Engineering, Kyushu University, Nishi-ku, Fukuoka 819-0395, Japan
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- Kazunari Yoshizawa
- Institute for Materials Chemistry and Engineering, Kyushu University, Nishi-ku, Fukuoka 819-0395, Japan
書誌事項
- 公開日
- 2008-11-14
- 資源種別
- journal article
- DOI
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- 10.1021/ja802618s
- 公開者
- American Chemical Society (ACS)
この論文をさがす
説明
Tyrosinase catalyzes the biological conversion of tyrosine to dopaquinone with dioxygen at the dinuclear copper active site under physiological conditions. On the basis of the recent X-ray crystal structural analysis of tyrosinase (J. Biol. Chem. 2006, 281, 8981), a possible mechanism for the catalytic cycle of tyrosinase is proposed by using quantum mechanical/molecular mechanical calculations, which can reasonably take effects of surrounding amino-acid residues, hydrogen bonding, and protein environment into account. The (mu-eta2:eta2-peroxo)dicopper(II) species plays a role in a series of elementary processes mediated by the dicopper species of tyrosinase. A stable phenoxyl radical is involved in the reaction pathway. The catalysis has five steps of proton transfer from the phenolic O-H bond to the dioxygen moiety, O-O bond dissociation of the hydroperoxo species, C-O bond formation at an ortho position of the benzene ring, proton abstraction and migration mediated by His54, and quinone formation. The energy profile of the calculated reaction pathway is reasonable in energy as biological reactions that occur under physiological conditions. Detailed analyses of the energy profile demonstrate that the O-O bond dissociation is the rate-determining step. The activation energy for the O-O bond dissociation at the dicopper site is computed to be 14.9 kcal/mol, which is in good agreement with a measured kinetic constant. As proposed recently, the His54 residue, which is flexible because it is located in a loop structure in the protein, would play a role as a general base in the proton abstraction and migration in the final stages of the reaction to produce dopaquinone.
収録刊行物
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- Journal of the American Chemical Society
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Journal of the American Chemical Society 130 (50), 16890-16897, 2008-11-14
American Chemical Society (ACS)
