Speaker:
Matthias Wilmanns, Ph.D.
Head of the Hamburg Unit of the European Molecular Biology Laboratory (EMBL)
Professor at the Hamburg University Clinical Center Eppendorf (UKE)
Program Description
Metabolons are temporary structural-functional complexes formed between sequential enzymes of a metabolic pathway. They are held together both by non-covalent interactions and by structural elements of the cell, such as integral membrane proteins and proteins of the cytoskeleton. In multi-enzymes with active site-connecting product/substrate tunnels there is an essential requirement for a metabolon-like structural organisation, as lack of tunnel sequestration generally leads to loss of catalytic activity. Our group has a long-standing interest in glutamine amidotransferases (GATases), which use reactive ammonia produced by the first GATase glutaminase and subsequently channelled to diverse synthase activities to become incorporated into a range of metabolites. During this process ammonia needs to be strictly sequestered from solvent, which otherwise would lead to immediate protonation and generate an inactive ammonium ion. To avoid wasteful consumption of metabolites, catalytic activity of GATases is controlled by a sophisticated arsenal of regulatory mechanisms. In this presentation, general common and diverse control mechanisms will be discussed, based on available biochemical and structural data. The latter will include data from our research infrastructures for advanced structural biology applications, which allow visualization of specific catalysis states at very short time intervals.
At the beginning of the presentation, I will give an outline overview on present capabilities of research infrastructures in structural biology operated by the European Molecular Biology Laboratory (EMBL) and provide information on the Life Science Alliance of Stanford University and EMBL.
