3D-structural elucidation of biologically important macromolecules.

Abstract

In 1953 Max Perutz discovered that the phase problem of protein crystallography could be solved by the method of isomorphous replacement with heavy atoms. At that time scientists expected that the structure, not only of haemoglobin, but also of many other proteins, would soon be solved. This did not happen. Only three protein structures had been solved by 1965, and only eleven by 1970. The practical difficulties of crystallization and data collection and, in addition, the enormous effort to interpret an electron density map at that time, made scientists reluctant to enter this risky new field. Today, the situation is transformed and more than 400 protein structures have been solved. Many of these structures are of practical interest to medicine, an interest that often becomes apparent after the solution of the protein. This paper is a brief review of the techniques being used in the field of crystallographic elucidation of macromolecular structures. In particular, some aspects of the structures of ribonuclease A, calmodulin and the human growth hormone-receptor complex are presented. These structures serve as examples and thus they represent the significance of the results which are normally obtained from a regular crystallographic investigation.