Determination of crystallographic structure of a mitochondrial serine protease HtrA2 under high hydrostatic pressure to characterize its con

The crystallographic structure of HtrA2, a mitochondrial serine protease involved in apoptosis, together with molecular simulation studies and viscosities analysis have revealed that the flexibility of two regulatory loops lining the active site is related to functional efficiency and to the high thermostability of the enzyme. The crystallographic structures of different mutants, either in a closed or open conformation, support the hypothesis that the flexibility of the loops surrounding the active site is necessary for catalytic efficiency. High hydrostatic pressure crystallography is an ideal technique to trap high energy transient conformers involved in enzymatic activity and/or interaction with partners. The analysis of the crystallographic structures of HtrA2 WT and various more rigid mutants under high hydrostatic pressure will allow us to identify precisely the determinants of HtrA2 plasticity related to its functional efficiency and high thermostability.