Toward fully fledged high-pressure macromolecular crystallography

Pressure allows one to explore the energy landscape and the various conformations of macromolecules. This might be one of the most interesting prospects of combining macromolecular crystallography (MX) with pressure perturbation. This paper presents innovations in high-pressure macromolecular crystallography (HPMX). A new-generation diamond anvil cell extends the technical feasibility of HPMX experiments up to about 2.5 GPa (depending on the sample). Thanks to the large useful aperture (82°) provided by this cell and special loading techniques (use of splinter and/or multiple samples), HPMX can now be more readily applied to crystals with very anisotropic habits and/or low-symmetry space groups, as demonstrated by analysis of diffraction data collected at 140 MPa from orthorhombic urate oxidase crystals. The behaviour of hexagonal crystals of an octanucleotide was investigated up to 2 GPa.