Assessing the progress of Mycobacterium tuberculosis H37Rv structural genomics

Abstract

Tuberculosis threatens human health nowhere more than in developing countries with large malnourished and/or immune-compromised (e.g. HIV infected) populations. The etiological agent, Mycobacterium tuberculosis (Mtb), is highly infectious and current interventions demonstrate limited ability to control the epidemic in particular of drug resistant Mtb strains. New drugs and vaccines are thus urgently required. Structural biologists are critical to the TB research community. By identifying potential drug targets and solving their three dimensional structures they open new avenues of identifying potential inhibitors complementing the screening of novel compounds and the investigation of Mtb's molecular physiology by pharmaceutical companies and academic researchers. Much effort has gone into structurally elucidating the Mtb proteome though much remains to be done with progress primarily limited by technological constraints. We review the currently available data for Mtb H37Rv to extract the lessons they have taught us. KeywordsMycobacterium tuberculosis, structural genomics, drug target AbbreviationsAll abbreviations in the manuscript are standard in the field.

Expression and production of soluble Mycobacterium tuberculosis H37Rv mycosin-3

“…Mtb proteins further incorporate more glycines, alanines, prolines and arginines than E. coli and the organism also has post-translational modification machinery that E. coli lacks [22] . Although saprophytic M. smegmatis is occasionally suitable for Mtb protein production, only a handful of successful cases of protein production have been reported [23] .…”

“…MycP 3 fusion protein, however, remained insoluble except when produced in Arctic Express. Although rarely used for Mtb H37Rv protein production [23] , Arctic Express successfully produced GST-tagged MycP 3 fusion proteins in significant quantity at low temperature despite lacking an N-terminal extension that stabilizes the catalytic domain [14] , [15] , [16] .…”

Functional, structural and epitopic prediction of hypothetical proteins of Mycobacterium tuberculosis H37Rv: An in silico approach for prioritizing the targets

“…We have found many of these proteins template are in TBSGC server and in published literature those may play key role in drug discovery/further analysis [119][120][121][122].…”

The crystal structure of the drug targetMycobacterium tuberculosismethionyl-tRNA synthetase in complex with a catalytic intermediate

“…A major structural biology effort has been made by many investigators to create a platform of crystal structures of key M. tuberculosis proteins to assist in the development of new therapeutic agents to treat tuberculosis patients (e.g. Murillo et al, 2007;Fang, van der Merwe et al, 2015;Terwilliger et al, 2003). Here, we describe the crystal structure of M. tuberculosis MetRS (…”