Rare earths as isomorphous calcium replacements for protein crystallography

Replacement of calcium in thermolysin by lanthanide ions has been found to provide a useful isomorphous derivative for the X-ray analysis of the protein. The substitution can be achieved simply by diffusion of the heavy metal ions into the native protein crystals and, as measured by crystallographic residuals, causes little disruption of the native conformation. This disruption is noticeably less when the radius of the lanthanide ion is less than that of calcium. The results suggest that lanthanide substitution may be a generally applicable method of obtaining isomorphous heavy atom derivatives of calcium binding proteins.