Direct phasing at low resolution of a protein copurified with human paraoxonase (PON1)

In this paper, the low-resolution structure of a previously unknown protein copurified with human paraoxonase (PON1) is reported. The structure of this protein was very difficult to solve using classical crystallographic methods. Progress was made using a new phasing method based on topological analysis. From the experimental point of view, this method has the advantage of requiring only a simple low-resolution X-ray data set. The program used and the different steps of the dataprocessing and phasing procedure are described. The results provided an insight into the failure of previous molecular-replacement attempts. The low-resolution shape of the protein which was presented with confidence is compared with and confirmed by the structure at 1.8 Angstrom solved subsequently using classical methods. This work shows that this direct-phasing method could be used systematically in difficult cases: it provides low-resolution structural information comparable with that obtainable by electron microscopy.