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 data-processing 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 A 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.