Profile

Lack of space within the premises of the Max Planck Institute of Biochemistry required to rent a laboratory in the IZB building across the road for the Emeritus Group Huber, which allows a small scale operation of protein preparation, crystallization and crystallography. An office is available in the MPI.
The group comprises a postdoctoral fellow and two PhD students supported by a ‘Robert Huber Nobelpreisträgerstipendium' of the MPG and the 'Peter und Traudl Engelhorn Stiftung', respectively.
Focus of this group's research work is on cage-forming regulated proteases and their regulatory components (proteasome, PAN, LON) and on secreted acidic proteases (SAP) of Candida albicans, virulence factors of the fungal pathogen.
In collaboration with Dr. Michael Groll (LMU) and several international Pharma and Crop Science companies we analyse the crystal structures of yeast proteasome ligand complexes to assist in drug design and the development of fungicides for crop protection. The discovery of the proteasome as a target for certain forms of myeloma and other forms of cancer has greatly stimulated the field.
PAN, an archaeal ATPase and proteasomal activator from S. solfataricus serves as a model for the ATPase sub-complex of the eukaryotic regulatory particle and may reveal the principal structural basis of proteasomal activation (Dr. Igor Siwanowicz). Many constructs were made with the aim to delete presumably flexible segments interfering with crystallization and some crystals were obtained.
The ubiquitous LON proteases have their protease and ATPase regulatory components fused on one polypeptide. Our construct and preparation is from the archaeon A. fulgidus. As only the protease part has been structurally defined so far, the holo-structure is expected to reveal the mechanism of activation (Dr. Igor Siwanowicz).

Of the more than ten iso-enzymes of the SAP family, we have expressed and crystallized and structures determined of SAP3 and SAP1 with and without bound substrate analog inhibitor in collaboration with Dr. C. Borelli and Prof. H. C. Korting (LMU).
As the fold of SAP2 was known, we aim at defining the isoenzymes’ structural diversity to explain their different substrate specificities.
A number of other projects and PhD theses, whose experimental parts were conducted in 2003 to 2005 have been completed and manuscripts are being written for publication:
- Seryl-tRNA synthetase of A. aeolicus (R. Willkomm with M.Wahl, Göttingen and M. Augustin, Proteros) liganded with substrate and product analogs;
- selenophosphate synthase (SelD) from various organisms, E. coli, A. aeolicus, Drosophila (Li-Chi Chang with M. Wahl, Göttingen).
Both projects are part of an extensive programme on the elucidation of the pathway and mechanism of selenocysteine biosynthesis in collaboration with Prof. A. Böck (LMU), where seryl-tRNA synthase and SelD catalyse the initial steps leading to selenocysteyl-tRNA^Sec; - eukarytic NTP-transferase from a human pathogen, Leishmania major (T. Steiner with R. Gerardy-Schahn, Hannover): Uridine diphosphate glucose pyrophosphorylase catalyses the formation of UDP-glucose, a key metabolite in carbohydrate pathways in all organisms.
The first and the last project provided high resolution crystal structures and allowed mechanistic interpretations, the second project gave crystals, so far with insufficient diffraction power only.

In 2005 a second spin-off biotech company SuppreMol was established and initial financing assured for this enterprise by an international investor. SuppreMol's business is to develop Fc receptors as therapeutic proteins offering a novel strategy to combat autoimmune diseases.