I
was born February 20, 1937 in München as the first child of Sebastian and
Helene Huber. My father was cashier at a bank and my mother kept the house and
brought up the children, me and my younger sister, a difficult task during the
war, a continuous struggle for some milk and bread and search for air-raid shelters.
There was no Grammar school in 1945 and 1946 and I entered the Humanistische
Karls-Gymnasium in München 1947 with intense teaching of Latin and Greek,
some natural science and a few optional monthly hours of chemistry. I learned
easily and had time to follow my inclination for sports (light athletics and
skiing) and chemistry, which I taught myself by reading all textbooks I could
get.I left the Gymnasium with the Abitur in 1956 and began to study chemistry at the Technische Hochschule (later Technische Universität) in München, where I also made the Diploma in Chemistry in 1960. A stipend of the Bayerisches Ministerium für Erziehung und Kultur and later of the Studienstiftung des Deutschen Volkes helped to relieve financial problems of my family and allowed me to study without delay. The most impressive teachers I remember were W. Hieber and the logical flow and impressive diction of his lectures in inorganic chemistry; E.O. Fischer, the young star in metalloorganic chemistry; F. Weygand and his deep knowledge of organic chemistry; and G. Joos and G. Scheibe, the physicist and physicochemist, respectively. I joined the crystallographer W. Hoppe's laboratory for my diploma work on crystallographic studies of the insect metamorphosis hormone ecdysone. Part of these studies were made in Karlson's laboratory at the Physiologisch-Chemisches Institut der Universität München, where I found by a simple crystallograpic experiment the molecular weight and probable steroid nature of ecdysone which Hoppe and I later elucidated in atomic detail after my thesis work which was on the crystal structure of a diazo compound (1963). This discovery convinced me of the power of crystallography and led me to continue in this field.
After a number of structure determinations of organic compounds and methodical development of Patterson search techniques I began in 1967, with Hoppe's and Braunitzer's support, crystallographic work on the insect protein erythrocruorin (with Formanek). The elucidation of this structure and its resemblance to the mammalian globins as determined by Perutz and Kendrew in their classical studies suggested for the first time a universal globin fold. In 1971 the University of Basel offered me a chair of structural biology at the Biozentrum and the Max-Planck-Gesellschaft the position of a director at the Max-Planck-Institut für Biochemie, which I accepted. I remained associated with the Technische Universität München, where I became Professor in 1976.
In 1970, I had begun work on the basic pancreatic trypsin inhibitor which has later become the model compound for the development of protein NMR, molecular dynamics, and experimental folding studies in other laboratories. Work in the field of proteolytic enzymes and their natural inhibitors has been continued and extended to many different inhibitor classes, proteases, their proenzymes, and complexes between them (with Bode, Bartels, Chen, Fehlhammer, Deisenhofer, Loebermann, Kukla, Papamokos, Ruhlmann, Steigemann, Toknoka, Wang, Walter, Weber, Wei) including recently inhibitors of cysteine proteases (with Musil, Bode, Engh) and other hydrolytic enzymes like a-amylase (whith Pflugrath, Wiegand) and creatine hydrolase (with Hoeffken). The potential of these systems for drug and protein design has spurred our interest until today.
Early in the seventies I initiated work on immunoglobulins and their fragments, which culminated in the elucidation of several fragments, an intact antibody and its Fc fragment, the first glycoprotein to be analysed in atomic detail (with Colman, Deisenhofer, Epp, Marquart, Matsushima). Work was extended to proteins interacting with immunoglobulins and to complement proteins (with Paques, Jones, Deisenhofer). We also studied a variety of enzymes leading to the elucidation of the structure and the chemical nature of the selenium moiety in glutathione peroxidase (with Ladenstein, Epp). We determined the structures of citrate synthase in different states of ligation (with Remington, Wiegand) and recently of a very large multienzyme complex, heavy riboflavin synthase (with Ladenstein).
Early in the 1 980s we began with studies of proteins involved in excitation energy and electron transfer, light-harvesting proteins (with Schirmer, Bode), later bilin-binding protein, the reaction centre (with Deisenhofer, Epp, Miki in collaboration with Michel) and ascorbate oxidase (with Messerschmidt, Ladenstein) which are described in my lecture.
Most of these structural studies were collaborative undertakings with other laboratories, many of them from foreign countries.
We had discovered that some of the proteins analysed showed large-scale flexibility which was functionally significant. The trypsinogen system was investigated (with Bode) in great detail by low temperature crystallography, gamma-ray spectroscopy, chemical modification, and molecular dynamics calculations. However, it required some years before the scientific community in general accepted that flexibility and disorder are very relevant molecular properties also in other systems.
The development of methods of protein crystallography has been in the focus of my laboratory's work from the beginning and led to the development of refinement in protein crystallography (with Steigemann, Deisenhofer, Remington), to the development of Patterson search methods (with Bartels and Fehlhammer), to methods and suites of computer programmes for intensity data evaluation and absorption correction (FILME, with Bartels, Bennett, Schwager), for protein crystallographic computing (PROTEIN, with Steigemann), for computer graphics and electron density interpretation and refinement (FRODO, Jones), and for area detector data collection (MADNES, Pflugrath, Messerschmidt). These methods and programmes are in use in many laboratories in the world today.
I married Christa Essig in 1960. We have four children. The eldest daughter (1961) and the two sons (1963, 1966) have been or are studying economics. The youngest daughter (1976) shows some interest in biology, a last hope.