The approach of the XMTB Structural Proteomics Consortium is based on the knowledge of the complete genome of Mycobacterium tuberculosis. It integrates a range of proteomics-oriented key technologies in the area of bioinformatics, screening of large ligands libraries, structural biology methods such as X-ray crystallography and NMR-spectroscopy, and proteomics based in vivo screening methods. We are aiming to determine 35 molecular structures of selected XMTB target proteins and 70 target – small molecular weight ligand. Five of these target proteins will be selected for the development of potential drugs.

Within the R&D part of the project, we are aiming to develop complementary structure-based high-throughput technologies using NMR spectroscopy and X-ray crystallography. While NMR is used to structurally map ligand binding sites on the selected targets, X-ray crystallography is applied for the determination of the target-ligand complex structures. Using these data, identified ligands are further investigated with the aim to directed drug discovery. The process is carried out by the combined application of structural proteomics methods and in vivo screens. To ensure the highest efficiency of this integrated approach a number of techniques and tools will be developed. A major focus is on the implementation of a large scale high-throughput crystallisation facility in Hamburg.