Insilico drug designing and Lead Compound validation against YycG histidine kinase

Shama Najir-Ahemad Mujawar, Priyanka Parhi, Sameer Chaudhary

Abstract


In bacteria, signal transduction in response to a wide variety of environmental stimuli is mediated by pairs of proteins that communicate with each other through a two-component signal transduction system (TCS) involving protein phosphorylation. TCS consists of a histidine kinase and a response regulator, which play global roles in bacterial growth as well as drug-resistance, virulence, biofilm formation, and regulation of receptors of plant hormones such as ethylene and cytokinine. TCSs are attractive antimicrobial targets considering various prospects. YycG/YycF which is highly conserved and specific to low G +C Gram positive bacteria, are essential for Bacillus subtilis and Staphylococcus aureus survival. Inhibitors of YycG histidine kinase, such as aranorosinol B, thiazolidinone, isothiazolone etc have been screened and documented against Bacillus subtilus. This prompted us to demonstrate that S. epidermidis possesses a homologous YycG/YycF TCS, and to investigate whether it would be an appropriate target for the design of novel antibacterial agents. In our study, these novel inhibitors ZINC00518229 (GLN299:HE22), ZINC0387112 (GLN229: HE22),  ZINC00014168 (HIS466:HD1),  ZINC13377075 (HIS466:HD1) of YycG histidine kinase show interaction with active site residues and  are considered as promising lead-compounds for developing new compounds against staphylococci infections.

Keywords


Histidine Kinase, TCS, Drug Designing, YycG/YycF, Docking, Insilico Analysis

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