Three-dimensional structure of human [¹¹³Cd₇]metallothionein-2 in solution determined by nuclear magnetic resonance spectroscopy

The three-dimensional structure of human [¹¹³Cd₇]metallothionein-2 was determined by nuclear magnetic resonance spectroscopy in solution. Sequence-specific ¹H resonance assignments were obtained using the sequential assignment method. The input for the structure calculations consisted of the metal-cysteine co-ordinative bonds identified with heteronuclear correlation spectroscopy, ¹H-¹H distance constraints from nuclear Overhauser enhancement spectroscopy, and spin-spin coupling constants ³J_HNαand³J_αβ. The molecule consists of two domains, the β-domain including amino acid residues 1 to 30 and three metal ions, and the α-domain including residues 31 to 61 and four metal ions. The nuclear magnetic resonance data present no evidence for a preferred relative orientation of the two domains. The polypeptide-to-metal co-ordinative bonds in human metallothionein-2 are identical to those in the previously determined solution structures of rat metallothionein-2 and rabbit metallothionein-2a, and the polypeptide conformations in the three proteins are also closely similar.