Structural model of rabbit liver copper metallothionein 

Abstract

Molecular modelling techniques have been used to calculate the structure for the primary, mammalian copper-containing protein, metallothionein Cu₁₂-MT. Structural information obtained from existing spectroscopic data and comparison with inorganic copper(I)–thiolate model compounds were employed. A two-domain structure, with stoichiometries of Cu₆S₉ and Cu₆S₁₁, was constructed in which the copper(I)–cysteine connections were based on the arrangement of the cysteines in the Zn₇-MT precursor as determined by previous ¹H NMR studies. In the minimized structure, in which metal–thiolate bond lengths and angles were allowed to vary, each copper(I) was trigonally co-ordinated by cysteine thiolates; the average bond length was calculated to be close to 224 pm. In the α domain of the protein both bridging (7S) and terminal (4S) thiolate ligation take part in the Cu₆S₁₁ cluster structure, in the β domain all nine thiolates bridge pairs of Cu^I atoms to form the Cu₆S₉ cluster structure. Significantly, the energy-minimized structure exhibits two main crevices that are similar to those reported for the structure of Cd₅Zn₂-MT 1 obtained by analysis of X-ray diffraction data. These crevices could allow access to the otherwise embedded copper–thiolate clusters.

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