Structural Biochemistry and Mechanisms

Structural Biochemistry and Mechanisms

The recent years of whole genome studies have enforced a view, in which most cellular constituents do not act in isolation, but as part of large assemblies. A large spectrum of biological reactions and tasks essential for the survival of cells are performed by these macromolecular complexes, also referred to as molecular machines. These biochemically labile assemblies are composed of either protein only, or proteins bound to nucleic acids (DNA or RNA). Prominent examples are the proteasome, the fatty acid synthase, the nucleosome, the ribosome, and the spliceosome. As cellular homeostasis is governed by macromolecular complex function, their mis-function is also a central cause for human disease, making the in-depth study of functional mechanisms essential for the investigation of disease etiology.

In our research, we apply mechanistic biochemistry and X-ray crystallography to study large macromolecular complexes involved in proteostasis and fatty acid metabolism. Owing to the labile nature and complexity of interrogating these molecular machines, we are engaged in the development of biochemical tools to purify and stabilize them, as well as arrest them in distinct functional states. We also develop methods for X-ray data collection, phasing, structure determination, and refinement of large complexes. To study dynamic aspects of their function we apply time-resolved approaches.


Press releases & research news

Fatty acid factory filmed at work

Researchers led by Ashwin Chari and Holger Stark have visualised the structure of this fatty acid factory at an unprecedented resolution of 1.9 Å. At this level of detail, they were able to directly observe enzyme reactions and track a complete fatty acid production cycle. The findings provide new approaches for combating pathogens and producing fatty acids sustainably. more

<p>Scientists identify promising COVID drug candidates</p>

A team of researchers, including Ashwin Chari's group from the MPI for Biophysical Chemistry, has identified several candidates for drugs against the SARS-CoV-2 coronavirus. Among them are two promising compounds that are currently being investigated in preclinical studies. This drug screening – probably the largest of its kind – also revealed a new binding site on the virus. more

<span>World record resolution in cryo-electron microscopy</span>

Holger Stark and his team have broken a crucial resolution barrier in cryo-electron microscopy. The scientists succeeded in observing single atoms in a protein structure and taking the sharpest images ever with this method. Such unprecedented details are essential to understand how proteins perform their work or cause diseases in the living cell. The technique can in future also be used to develop active compounds for new drugs. more

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