The work in our lab is devoted to the understanding of the biophysical principles underlying protein-ligand interactions which can be used for drug profiling and assay development. The biopharmaceutically relevant ligands thus investigated are glycosaminoglycans (see Figure) which represent a class of linear, highly charged carbohydrates involved in a number of (patho-)physiological processes like inflammation, angiogenesis, cancer, etc. The protein receptors for these complex molecules are in the process of being identified by proteomics and bioinformatics tools as potential targets for the development of novel therapies. The design and synthesis of bioactive lead compounds is carried out in the framework of strong in-house and international collaborations. Biotechnology is used, on the one hand, to produce recombinant glycosaminoglycan-binding proteins in bacterial and eukaryotic expression systems and, on the other hand, to bioassay lead compounds in situ. A long-term future goal is to biotechnologically produce GAGs and GAG analogues by using recombinant biosynthetic enzymes.
Protein Members of Our Group:
Interleukin-8 (IL-8) is an inflammatory chemokine which promotes the accumulation and activation of neutrophil leukocytes and which has been implicated in a wide range of acute and chronic inflammatory diseases. Studying ligand binding to IL-8 and determining the structure of the corresponding protein-ligand complexes is a major goal of our lab, since finding inhibitors of this interaction would represent a major step forward in treating inflammatory diseases.
The tyrosine repressor (TyrR) is a bacterial protein which is responsible for transcriptional regulation of the biosynthesis and transport of aromatic acids.  Understanding the structural principles of prokaryotic transcriptional regulation is a major task in our lab. Of special interest is the multidomain character of TyrR, which enables us to study the binding of activators and ligand separately by the generation of truncation mutants.
The human vitamin D3 receptor (hVDR) is a nuclear transcription factor which is responsible for regulating the expression of genes involved in calcium metabolism. Like TyrR, hVDR is a multidomain protein which is active in vivo mainly as a heterodimer (by binding to monomers of other members of the nuclear receptor family) and only rarely as a homodimer. The biophysical characterisation of the hVDR domains as well as of the full length protein with respect to binding of its ligands is in the focus of our lab.
The enzyme nitric oxide synthase (NOS) generates NO from L-arginine and oxygen in a reaction involving several cofactors and prosthetic groups, including NADPH, FAD, FMN, tetrahydrobiopterin, and heme. Spectroscopy of these chromophoric groups is used to obtain structural and dynamic information of this important enzyme
The HIV-1 protease belongs to the class of aspartic proteases and is responsible for the proteolytic cleavage of two precursor polypeptides encoded by the gag and the pol viral genes. Since a wealth of structural information is available on this enzyme itself as well as on several inhibitor complexes, we are concentrating on studying the conformational dynamics of protease-inhibitor complexes by time-resolved spectroscopy and molecular dynamics computer simulations.