NEW DEVELOPMENTSIN PROTEIN CRYSTALLOGRAPHY

Protein crystallography is currently undergoing a rapid change in many different ways. One development is the explosion of interest by molecular biologists and immunologists since knowledge of protein sequences, obtained via DNA sequencing, is expanding rapidly, but does often not increase immediately insight into the functioning of the protein. Another change is the recombinant DNA technique which make it possible to obtain large amounts of proteins which were previously only available in minute quantities. A third change is the wide-spread awareness that detailed knowledge of wellselected protein structures is a promising starting point for designing new pharmaceuticals and vaccines, for obtaining new proteins via protein engineering techniques and for inspiring synthetic chemists in their biomimetic endeavours. At the same time many technical aspects of protein crystallography are undergoing a rapid development. Someof them will be describedin this paper. Crystal structures of proteins can be obtained currently in two quite different ways: (i) the "multiple isomorphous replacement" (MIR) method [1-3] for de novo structure determinations, often using additional anomalous scattering information (MIRAS) [4,5]; and, (ii) the "molecular replacement" (MR) method [6-8] for solving new structures related to a known structure. We will discuss the steps involved in obtaining high resolution X-ray structures as outlined in Figure 1. A detailed account of these steps can be found in two volumes of Methods of Enzymology [9]