Trimethyllead acetate: a first-choice heavy atom derivative for protein crystallography

The three-dimensional conformation of a protein provides a wealth of biochemical information and with the advent of cloning techniques that allow the preparation of proteins almost at will, a renewed interest has arisen in the crystallographic determination of protein structures. As in any research technique, however, there are often many difficulties encountered in an X-ray crystallographic investigation. One of these is the "phase problem." Although in recent years there has been considerable progress in the development of techniques for phase determination, including the use of molecular replacement and multiple wavelength measurements, the multiple isomorphous replacement method is still the most successful method for obtaining a three-dimensional structure. Here we report the use of trimethyllead acetate as a heavy atom compound of first choice in the preparation of an isomorphous heavy atom derivative.