Biochemistry and Structural Biology of Cwp84, a conserved cysteine protease from C. difficile

  • Nüß, Dorota, (Projektleitung)

    Projektdetails

    Beschreibung

    Clostridia comprise a large family of ubiquitously occurring, anaerobic, sporulating bacteria. Of particular interest is the C. difficile-specific Cwp84, a surface-bound cysteine protease conserved within all strains of C. difficile. We discovered that the 82 kDa protease Cwp84 contains a segment with significant homology to papain-like proteases; this assignment provides a consistent explanation of the observed intermediates during auto-degradation. Together with a preliminary assignment of the Cwp84 domain architecture, we established a framework to systematically study the so far poorly understood biochemistry of the enzyme.
    Specifically, we will investigate the domain organisation of Cwp84 and we will reveal the activation mechanism. Secondly, we will investigate the catalytic mechanism of the enzyme. Thirdly, we will determine the crystal structures of relevant domains of Cwp84. The combined data shall reveal the detailed mechanism of activation as well as important substrate recognition elements. This knowledge will be further exploited to design optimised active site-directed inhibitors, which represent a starting point for the development of specific diagnosis and therapy options against C. difficile infections.



    In the structural biology laboratory, headed by Prof. Hans Brandstetter, we have state-of-the-art equipment and methods for performing molecular biology, biochemistry, biophysics and X-ray crystallography available.
    KurztitelBiochemistry and Structural Biology of Cwp84 protease
    StatusAbgeschlossen
    Tatsächlicher Beginn/ -es Ende1/10/1030/09/15

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