| Citation | Huber has built up, led and still leads the most productive protein crystallography laboratory in Europe. His own contributions to crystallography, made over a period of some 25 years, are prodigious. For his Ph. D. thesis he solved the chemical formula of the important insect hormone ectyson which had eluded the chemists. He then demonstrated that the tertiary fold of the polypeptide chain in the haemoglobin of the fly larva chironomus closely resembled that in Kendrew's sperm whale myoglobin, indicating for the first time that this fold had been preserved throughout evolution.
Huber's next achievement was the solution of the structure of trypsin inhibitor and the demonstration that in its complex with trypsin it mimicked the tetrahedral transition state of the enzyme's substrate. Since then he has determined the structures of many other proteinases, their inactive precursors and their inhibitors, and has established himself as the world authority in this field. Outstanding structures are tgise if oricarboxypeptidase, which led to the discovery of the remarkable activation mechanism of this enzyme, and of the complex of thrombin with hirudin, which showed the molecular mechanism of inhibition of blood clotting by this leech toxin.
In parallel with this work, Huber solved the structures of several immunoglobulin fragments. He was the first to determine the structure of the complement-activating F-fragment, which was alkso the first variable and the first constant domains in Fab-fragments.
Huber's structure of citrate synthase revealed a striking example of aconformational change undergone by an enzyme on combinationwith its substrate bya process of induced fit.
Huber shared the Nobel Prize for Chemistry in 1988 with Michel and Deisenhofer for their detrermination of the remarkable and supremely important structures of thephotchemical reaction centre of Rhodopseudomonas viridis and of phycocyanin, the light harvesting protein of the blue-green alga Mastiglocadus laminosus. This protein binds linear tetrapyrroles in a tertiary fold reminiscent of the globins, which brought Huber back full circle to his first structure, erythrocruerin,
Huber has also determined the structures of several copper-containing electron-transfer proteins, including that of ascorbate oxidase, and of other metallo-enzymes. These studies have thrown new light on electron-transfer systems and on zinc coordination in proteins. He has also solved the structure of an important class of calcium binding proteins - the annexins. Finally his very accurate structures have provided important insights into the different degrees of mobility within protein molecules.
Huber has published some 400 papers. |