X-ray crystallography is the most important method for the determination of three-dimensional structures of bio-macromolecule. The information derived from crystal structures allows understanding of the catalytic mechanism of enzymes at the atomic level and predicting of the structure of small inhibitors, which may eventually become important drugs.

If the function of natural enzymes is understood in detail, it is possible to change biochemical properties such as the substrate specificity by site-directed mutagenesis of the underlying gene. Of particular interest are modifications of product spectra as, for example, that of a cyclodextrin generating enzyme, which was achieved in 1998. Such mutants were expressed, purified and functionally as well as structurally characterized.

Outer membrane proteins became a field of interest after we published the first structure of such a protein in 1990, which was then the second crystal structure of a membrane protein. Because of their large hydrophobic surfaces, membrane proteins require special purification and crystallization procedures as, for instance, detergents have to be added for preventing protein aggregation. The respective methods were then developed.

A further field of interest was the internal motions of enzymes that are required for catalysis. In 1995 we produced the first movie based on a dozen different chain fold conformations of adenylate kinase-type enzymes frozen in different crystal packings. Internal motions were the subject of a number of later publications.

Protein associations in experiment and theory became a further field of interest. In particular, we introduced protein surface mutations for crystallization in 1999, which became later known as ‘surface entropy reduction’. The recent publication explaining homo-oligomeric symmetry (2009) follows a number of theoretical concepts published over the years: structure prediction from the sequence and chain fold topology in 1974, sequence plasticity and energetic counterweight principle for ligand binding in 1979, complementarity in protein associations in 1984, substrate-phosphoryl group binding to the backbone in 1986, the selectivity of porins via binding sites and their electric polarity separator in 1992, and the formation of the steroid scaffold in 2004.