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South African biophysicists make important advance in fight against tuberculosis

from NSBP via South African Institute of Physics and University of Cape Town

From Oct. 27, 2012: The World Health Organization has declared tuberculosis infection to be a global health emergency. It is a major complication in HIV pathology, urban poverty as well as in rural settings. A specific anti-TB drug would be an important new clinical modality to treating TB infections . And rational drug design informed by protein biophysics research would be very useful in continuing the decline of TB deaths; just as it has been in development of anti-HIV drugs. In a paper in the biological crystallography section of Acta Crystallographica, a team of biophysicists in South Africa report a significant advance towards rational anti-TB drug design. The zinc-dependent enzyme, N-acetyl-1-d-myo-inosityl-2-amino-2-deoxy-d-glucopyranoside deacetylase (MshB) is important in the survival of the tuberculosis bacteria. Inhibit this enzyme and the infection could effectively be stopped. The South African team was able to grow protein crystals that diffract to 1.95 angstroms. Their images present a compelling view of the enzyme's active site, and the researchers were able to determine the stereoelectronic and dynamic roles of specific amino acids in the active site. Importantly, in this work they found that glycerol could be competitive inhibitor of this enzyme. more

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