3W6Q

Crystal structure of melB apo-protyrosinase from Asperugillus oryzae

Summary for 3W6Q

• Entry DOI: 10.2210/pdb3w6q/pdb
• Related: 3W6W
• Descriptor: tyrosinase (2 entities in total)
• Functional Keywords: four helix bundle, metal binding protein, oxidoreductase
• Biological source: Aspergillus oryzae
• Total number of polymer chains: 4
• Total formula weight: 285458.31

Authors

Fujieda, N.,Yabuta, S.,Ikeda, T.,Oyama, T.,Muraki, N.,Kurisu, G.,Itoh, S. (deposition date: 2013-02-20, release date: 2013-06-19, Last modification date: 2024-03-20)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.052 Å)