Laboratory of Structure and Function of Biomolecules

Application of structural and biophysical techniques on enzymes, receptors and bacterial transcription system.

Group leader: Ing. Jan Dohnálek, Ph.D.

Ing. Jan Dohnálek, Ph.D.Detailed laboratory website: https://sites.google.com/site/pragueprotein/

Physiological function of a biological macromolecule (protein, nucleic acid, complex), is tightly connected with its three-dimensional structure. We apply physical methods to determine the three-dimensional structure of such molecules and to measure other properties important for their function. In connection with functional data we aim at explaining the ultimate role of such molecules in the context of cell, tissue or organism. Where possible, conclusions are drawn towards biomedical or biotechnological applications.

Target molecular systems

We perform structure-function analysis of new enzymes or enzymes with the potential of novel applications, including sugar-nonspecific nucleases, metal-dependent oxidoreductases, flavin-dependent oxidoreductases and proteases. Most of these projects are targeted towards potential applications (food industry, dry goods, waste remediation, etc.), some have also potential for utilization in medicine. Our collaborators include Novozymes A/S, Denmark, and the laboratory of Petra Lipovová (University of Chemistry and Technology, Prague).

We are also involved in research on natural killer cell surface receptors. In collaboration with the team of Ondrej Vanek (Charles University) we investigate structural properties and complex formation of mammalian NK receptors and their ligands, with implications for mammalian immunology and potential treatment of cancer or viral infections.

Results of structure-function studies of bacterial transcription machinery can be utilized in fight against pathogenic bacteria (collaboration with Libor Krásný, Institute of Microbiology, Czech Academy of Sciences).

Our research tools

  • Recombinant production of proteins of interest, protein purification and characterization
  • X-ray crystallography, Cryo-electron microscopy, Small angle X-ray scattering (SAXS)
  • Biophysical techniques
  • Spectroscopic methods

 

Crystallization of biomolecules and X-ray diffraction experiments are performed in the Centre of Molecular Structure at our Institute, using our D8 Venture diffractometer with MetalJet X-ray source and SAXS experiments using a SAXSPoint 2.0 with MetalJet X-ray source and Eiger X-ray detector. More advanced experiments are done at European synchrotron radiation sources.

Methods development, teaching and central structural biology facilities

A part of our effort is dedicated towards development of X-ray crystallography methods (crystallization, data processing, phase problem solution, structure refinement, and model validation) and teaching at Prague universities, with the main focus on structural methods.

Since 2008 we have been involved in the design of the Centre of Molecular Structure, IBT, Biocev (central facilities for structural biology), its funding, operation, upgrades, and integration in the Czech Infrastructure for Integrative Structural Biology and the European infrastructure Instruct-ERIC.

More info:
https://sites.google.com/site/structuregallery/
https://sites.google.com/site/pragueprotein/