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| Mycobacterial Structural Genomics at the Pasteur Institute: Status report | |
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Tuberculosis has become a world health problem with its resurgence in
the past two decades causing 3 million deaths annually. In order to
develop new anti-tuberculosis drugs, however, scientists must have a
better comprehension of the biology behind mycobacterial infections
and intracellular survival. Towards this goal, the Pasteur Institute
has sequenced several mycobacterial genomes and launched a programme
to develop an integrated approach towards genomic analysis. This
combines functional genomics, (bio)chemistry, structural genomics,
bioinformatics, proteomics and immunology. The explicit aims are to
precisely define the proteome, pinpoint species-specific diagnostic
antigens, identify novel drug targets and screen for and develop
the cognate inhibitors. Within this context, the goal of the
structural genomics initiative is to determine the 3-dimensional
structures of many important mycobacterial proteins, which are
selected either as virulence factors, as essential for growth,
or as highly conserved and specific to mycobacteria. These proteins
represent new potential therapeutic targets for the design of
anti-tuberculosis drugs. Already, with the aid of synchrotron
radiation and anomalous diffraction methods, a number of crystal
structures of mycobacterial proteins have been determined,
including many of unknown function. And yet this is only a
beginning as, this structural genomics initiative will not limit
itself simply to the study of individual proteins, but will
also consider how specific proteins interact with each other and
their environment. Together, the information from these genomic
analyses will provide a means of discovering novel drug targets
and developing new anti-mycobacterial drugs.
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