Ta₆Br₁₄ is a useful cluster compound for isomorphous replacement in protein crystallography

The metal cluster Ta₆Br₁₄ has been used to prepare heavy-metal derivatives of two large proteins, ribulose-1,5-bisphosphate carboxylase/oxygenase and transketolase. In both cases, this cluster compound produced a single-site derivative for which a difference Patterson map, calculated to 5.5 Å resolution, could be solved straightforwardly. Ta₆Br₁₄ provided enough phase information to unambiguously locate the heavy-atom positions in other multiple-site derivatives. In transketolase, the heavy-metal complex binds at the surface of the protein in a dominantly hydrophobic pocket. In ribulose bisphosphate carboxylase/oxygenase, it binds between two molecules in the crystal lattice. There are negatively charged glutamic and/or aspartic acid residues in the vicinity of the bound clusters. Ta₆Br₁₄ is useful over a wide range of pH. For large proteins and/or large unit cells, this compound should be included in the initial screening for heavy-metal derivatives.