Advances in Mycobacterium tuberculosis Structural Genomics: Investigating Potential Chinks in the Armor of a Deadly Pathogen

N.      Chim; L.   M.   McMath; M.      Beeby; C.   W.   Goulding

Abstract

The waning effectiveness of established tuberculosis treatments due to the rise of multi and extensively drugresistant strains of Mycobacterium tuberculosis, coupled with the synergism of HIV infection, demands basic research efforts to inform focused drug development programs. Structural genomics projects provide rich sources of information for the rational design of anti-tubercular drugs, aiming to exploit unique and novel protein features and interactions based on atomic resolution structures. This review compiles structures of M. tuberculosis proteins elucidated since January 2007 that are promising avenues for drug design, encompassing proteins involved with known and experimental antituberculosis drugs, metabolism, dealing with the hostile environment of the host organism, and information processing.

Keywords: Tuberculosis, Mycobacterium tuberculosis, structural genomics, protein drug targets, X-ray crystallography