The tuberculosis structural genomics consortium: a structural genomics approach to drug discovery

Structural genomics is changing the way we study and understand biological systems, providing insight into the biology and life cycle of an organism at the molecular level through determination of protein structures. Structural genomics can be a particularly useful tool in the study of infectious diseases, especially to facilitate the development of new chemotherapeutics by providing a structural foundation for drug discovery. The Tuberculosis Structural Genomics Consortium (TBSGC) is applying a structural genomics approach to solving the structures of biologically and medically important proteins in the pathogenic bacterium Mycobacterium tuberculosis, adding to the scientific knowledge base essential for developing novel and effective antitubercular drugs. Tuberculosis (TB) has been declared a global health emergency by the World Health Organization (WHO). With the rise in the number of multidrug resistant (MDR) and extensively drug resistant (XDR) TB strains, the need for more effective TB treatments has become urgent. In contrast to other structural genomics projects, the TBSGC specifically prioritizes proteins based on their potential as drug targets. We describe the consortium's high-throughput (HT) structure determination pipeline that enables an efficient distribution of resources while also incorporating knowledge from several scientific fields. The success of this pipeline is illustrated in the number of successful structure solutions as demonstrated in the case studies presented in this chapter.