STRUCTURAL MODEL OF RABBIT LIVER COPPER-METALLOTHIONEIN

Molecular modelling techniques have been used to calculate the structu re for the primary, mammalian copper-containing protein, metallothione in Cu-12-MT. Structural information obtained from existing spectroscop ic data and comparison with inorganic copper(I)-thiolate model compoun ds were employed. A two-domain structure, with stoichiometries of Cu6S 9 and Cu6S11, was constructed in which the copper(I)-cysteine connecti ons were based on the arrangement of the cysteines in the Zn-7-MT prec ursor as determined by previous H-1 NMR studies. In the minimized stru cture, in which metal-thiolate bond lengths and angles were allowed to vary, each copper(I) was trigonally co-ordinated by cysteine thiolate s; the average bond length was calculated to be close to 224 pm. In th e alpha domain of the protein both bridging (7S) and terminal (4S) thi olate ligation take part in the Cu6S11 cluster structure, in the beta domain all nine thiolates bridge pairs of Cu-1 atoms to form the Cu6S9 cluster structure. Significantly, the energy-minimized structure exhi bits two main crevices that are similar to those reported for the stru cture of Cd5Zn2-MT 1 obtained by analysis of X-ray diffraction data. T hese crevices could allow access to the otherwise embedded copper-thio late clusters.