Martin Schmeing

Biography

2009 – Postdoc, LMB Cambridge 2004 – PhD, Yale University

Research Interest

The Schmeing lab is interested in large macromolecular machines that perform important cellular processes. These enzymes often require supramolecular organization and complex architecture to function. For example, both the ribosome and some non-ribosomal peptide synthetases use more than 100,000 atoms to make peptide bonds, while the proteases that break these bonds can be very small. Of course, these assemblies require regulation, processivity and fidelity, which contribute to their increased size. Our lab investigates both the manner by which cellular machines achieve these roles, and the mechanisms of their principal functions. To do this, we combine X-ray crystallography, electron microscopy and biochemical techniques. A. Structural Studies of Non-Ribosomal Peptide Synthetases Non-ribosomal peptide synthetases (NRPS) are large macromolecular machines that also catalyze peptide bond formation. Instead of making proteins, these enzymes produce a large variety of small molecules with important and diverse biological activity. For example, NRPSs synthesize anti-fungals, anti-bacterials, anti-virals, anti-tumourigenics, siderophores, and immunosuppressants including well-known compounds such as penicillin and cyclosporin. NRPSs use assembly line logic, with dedicated active sites for each amino acid added to the peptide. Single subunit NRPSs can be over 2 megadaltons, and are nature’s largest known enzymes. B. Structural Studies of the Ribosome The ribosome is the cell’s protein factory. It translates the genetic information in mRNA into protein, rapidly and with high fidelity, using aminoacyl-tRNAs as substrates. A large number of accessory protein factors are necessary for in vivo protein synthesis, and the interplay between these factors and the ribosome is extremely complex. Deregulation of protein synthesis in humans in associated with cancers, and many important antibiotics target the bacterial ribosome.