Research at the division of Molecular Structural Biology covers a broad range of topics, from structural enzymology, molecular neurobiology to the structural basis of glycoprotein export from the endoplasmatic reticulum.
Structural enzymology of the biosynthesis of polyketide antibiotics (Gunter Schneider): Anthracyclines are secondary metabolites of Streptomyces, and members of this class of polyketide antibiotics belong to the most-used chemotherapeutic agents in the combat against cancer. The research program aims at the elucidation of the structural enzymology of anthracycline biosynthesis. Target selection is focused on enzymes not related in sequence to proteins of known structure, and/or novel enzymatic mechanisms.
Structural biology of bacterial pathogens (Gunter Schneider): This research project aims at the structural and functional characterization of proteins and protein complexes from major pathogens, in particular Pseudomonas aeruginosa (for more details see http://www.aeropath.eu/) and Mycobacterium tuberculosis. One of the objectives of this program is to provide sufficient structural and mechanistic insights to facilitate the design of strong binding inhibitors, which may be developed into novel drugs.
Receptor mediated export of glycoproteins from the ER (Ylva Lindqvist): ERGIC-53 (LMAN1) is a protein which cycles between the endoplasmic reticulum and the ER-Golgi Intermediate Compartment. Mutations in ERGIC-53, or in its co-receptor MCFD2, cause a bleeding-disorder, combined deficiency of coagulation factors V and VIII. Both ERGIC-53 and MCFD2 can be cross-linked to factor VIII, suggesting that a tertiary complex is required for cargo specificity and we want to elucidate the molecular background.
Structural studies of proteins involved in lipid metabolism (Ylva Lindqvist): The intent in this project is to study enzymes in the biosynthesis of fatty acids and in the metabolism and signaling of their lipid derivatives with respect to 3D-structure, mechanism and specificity.
Nucleotide metabolism (Doreen Dobritzsch): Uracil and thymine are building blocks of pyrimidine nucleotides, which play a key role in the energy metabolism and numerous biochemical processes. In most organisms, the degradation of uracil and thymine is achieved by the three-step reductive reaction sequence. Our goal is to elucidate the molecular mechanisms of pyrimidine catabolism in humans.
Structural neurobiology (Bernhard Lohkamp): The research interest focuses on protein-protein complexes involved in nerve cell development, especially the axon and axon specification, and its implication in disease and nerve cell repair. A number of complexes constituting a variety of proteins (e.g. enzymes, motor proteins) are under structural and functional investigation. Furthermore I am involved in crystallographic methods development, especially graphical model building (Coot).
Protein-protein interactions in the ER (Jodie Guy): We focus on the multi-protein complexes that assist in the folding, modification, sorting and quality-control of newly-synthesised proteins in the eukaryotic endoplasmic reticulum (ER). Our goal is to use X-ray crystallography, together with biochemical and biophysical studies, to build detailed pictures of the structures, functions and interactions of these proteins.
Research at the division is supported by Karolinska Institutet, the Swedish Science Council (VR), VINNOVA
and the European Commission through Framework 6 & 7.