PNNL

Abstract

Mycobacterium tuberculosis is the etiological agent responsible for tuberculosis (TB), a chronic infectious disease that killed approximately 1.6 million people and infected another 8-9 million in 2008. Indeed, it is estimated that one-third of the human population has been infected with this gram-positive tubercle bacillus with most of these cases in 22 “high-burden” nations where the disease is endemic . While effective public health care systems keeps TB under control in the Western world, the emergence of multi-drug and extremely drug-resistant M. tuberculosis strains could result in a sudden loss of this control. Consequently, there is an urgency to develop a new generation of intervention strategies to treat and control TB. One current tactic is to focus on better understanding the molecular biology of the M. tuberculosis gene products, especially with regards to the interaction of virulence factors in the microenvironment in the host. One potential virulence factor is the protein Rv0577. A biological function for this 261-residue protein has not yet been identified, however, it has been associated with the methylglyoxal detoxification pathway. More importantly, Rv0577 has been shown to be the responsible component for neutral red staining of virulent strains of M. tuberculosis. Such a correlation, coupled with the isolation of Rv0577 in M. tuberculosis culture filtrates, suggests that Rv0577 may be a virulence factor. To assist function identification and structure-based drug design that targets Rv0577, a structure for this protein has recently been determined using X-ray diffraction methods and deposited in the RBSC PDB (3OXH). Once the coordinates for the structure of Rv0577 are released the amide chemical shift assignments presented here will facilitate chemical shift perturbation studies and assist in the identification of ligand binding surfaces on the protein.