Open and compressed conformations of <i>Francisella tularensis</i> ClpP

Caseinolytic proteases form large oligomeric assemblies responsible for maintaining protein homeostasis in bacteria and in so doing influence a wide range of biological processes. The caseinolytic protease subunit P (ClpP) represents a potential target for therapeutic intervention in pathogenic bacteria. Here, we detail an efficient protocol for production of recombinant ClpP from Francisella tularensis, and the structural characterization of three crystal forms. The structures reveal an open and a compressed state, and the inferred conformational changes that give rise to differences in the enzyme active site. Protocols for the supply of pure protein, crystallographic models and reproducible crystallization conditions can now support a structure-based approach to inhibitor development