3W6W

Crystal structure of melB holo-protyrosinase from Asperugillus oryzae

3W6W の概要

• エントリーDOI: 10.2210/pdb3w6w/pdb
• 関連するPDBエントリー: 3W6Q
• 分子名称: Tyrosinase, COPPER (II) ION (3 entities in total)
• 機能のキーワード: four helix bundle, metal binding protein, oxidoreductase
• 由来する生物種: Aspergillus oryzae
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 142983.34

構造登録者

Fujieda, N.,Yabuta, S.,Ikeda, T.,Oyama, T.,Muraki, N.,Kurisu, G.,Itoh, S. (登録日: 2013-02-22, 公開日: 2013-06-19, 最終更新日: 2024-03-20)

主引用文献

Fujieda, N.,Yabuta, S.,Ikeda, T.,Oyama, T.,Muraki, N.,Kurisu, G.,Itoh, S.
Crystal structures of copper-depleted and copper-bound fungal pro-tyrosinase: insights into endogenous cysteine-dependent copper incorporation.
J.Biol.Chem., 288:22128-22140, 2013

PubMed Abstract: Tyrosinase, a dinuclear copper monooxygenase/oxidase, plays a crucial role in the melanin pigment biosynthesis. The structure and functions of tyrosinase have so far been studied extensively, but the post-translational maturation process from the pro-form to the active form has been less explored. In this study, we provide the crystal structures of Aspergillus oryzae full-length pro-tyrosinase in the holo- and the apo-forms at 1.39 and 2.05 Å resolution, respectively, revealing that Phe(513) on the C-terminal domain is accommodated in the substrate-binding site as a substrate analog to protect the dicopper active site from substrate access (proteolytic cleavage of the C-terminal domain or deformation of the C-terminal domain by acid treatment transforms the pro-tyrosinase to the active enzyme (Fujieda, N., Murata, M., Yabuta, S., Ikeda, T., Shimokawa, C., Nakamura, Y., Hata, Y., and Itoh, S. (2012) ChemBioChem. 13, 193-201 and Fujieda, N., Murata, M., Yabuta, S., Ikeda, T., Shimokawa, C., Nakamura, Y., Hata, Yl, and Itoh, S. (2013) J. Biol. Inorg. Chem. 18, 19-26). Detailed crystallographic analysis and structure-based mutational studies have shown that the copper incorporation into the active site is governed by three cysteines as follows: Cys(92), which is covalently bound to His(94) via an unusual thioether linkage in the holo-form, and Cys(522) and Cys(525) of the CXXC motif located on the C-terminal domain. Molecular mechanisms of the maturation processes of fungal tyrosinase involving the accommodation of the dinuclear copper unit, the post-translational His-Cys thioether cross-linkage formation, and the proteolytic C-terminal cleavage to produce the active tyrosinase have been discussed on the basis of the detailed structural information.

PubMed: 23749993
DOI: 10.1074/jbc.M113.477612

実験手法

X-RAY DIFFRACTION (1.394 Å)