Glutamine Synthase Expression Profiling and Selective Inhibitor for Burkholderia psuedomallei K96243: An In-silico Approach
Abstract:
Melioidosis is a potentially fatal infection caused by
the Gram-negative bacillus, Burkholderia pseudomallei following an encounter
with contaminated soil or surface water. This study was to identify the highly
expressed gene in Burkholderia pseudomallei and model the target protein's
three-dimensional structure. Further, the study was intended to determine the
better binding candidates from the existing drugs against the target protein
for melioidosis. The highly expressed gene was identified by KEGG pathway and
their target protein was modeled using homology modeling. The modeled structure
was validated by PROCHEK and it can be further used for docking studies against
existing antibacterial drugs using Argus Lab. The ADME properties of drugs were
analyzed by the ADME/Tox WEB. The results revealed that, glutamine synthetase
was highly expressed in Burkholderia pseudomallei and its 3D model was
generated. The structure validation revealed that, the structure was reliable
and reasonable. The docking studies revealed that the Chloramphenicol compound
has higher docking score against the protein glutamine synthetase compared to
other existing compounds. The acceptable range of the ADME and biological
activity prediction of Chloramphenicol compound depicts better pharmacological
properties and possible drug-likeliness. This study concluded that, the
compound Chloramphenicol may be a better inhibitor for glutamine synthetase
protein. This compound may lead to development of effective drug against
Melioidosis.
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