Structural Proteomics of Myobacterium Tuberculosis
EMSL Project ID
2182a
Abstract
Project Description: Due to the availability of the complete genome of M. tuberculosis and also in part to our development of a genetic system for studying gene function in M. tuberculosis, our understanding of M. tuberculosis is advancing rapidly and will allow us to accurately target proteins based on their importance in virulence, persistence, reactivation, and overall viability of the organism. Targeting of functionally important proteins:We are emphasizing structure determination of proteins known to be functionally important for pathenogenicity, although the precise function will in many cases not be known at the time structure determination is begun. It is our intent that the structures we determine will be useful not only as contributions to a database of folds and functions, but also as a basis for an in-depth understanding of biological processes. We view this targeting strategy as a key to maximizing the scientific returns from this structural genomics project. Accordingly, we are targeting based on known function, genetic screens, informatics and interest from the M. tuberculosis research community.NMR work:High throughput methods for engineering proteins with high solubility and expression allows for the ready determination of 3D structures by solution NMR spectroscopy. We are requesting 6 weeks of 600 MHz NMR time in order to determine the structures of two proteins of M. tuberculosis which are functionally significant. The first hypothetical protein, coded by gene Rv2595, belongs to a cluster of orthologous groups of proteins (COG) which are regulators of stationary/sporulation gene expression and is an 81 residue protein. The second hypothetical protein, coded for by gene Rv1390, belongs to a COG which contains DNA-dependent RNA polymerase subunits and is a 111 residue protein. These proteins have many orothologues, but no sequence similarity to proteins with known 3D structure making them ideal for structural studies.
Project Details
Project type
Capability Research
Start Date
2004-04-16
End Date
2005-01-26
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members
Related Publications
G.W. Buchko, C-Y. Kim, T.C. Terwilliger, and M.A. Kennedy (2006) Solution structure of the conserved hypothetical protein Rv2302 from the bacterium Mycobacterium tuberculosis. J. Bacteriol., 188:5993-6001.