Structural elucidation of SrtA enzyme in Enterococcus faecalis: an emphasis on screening of potential inhibitors against the biofilm formation.

نویسندگان

  • Chandrabose Selvaraj
  • Jeyachandran Sivakamavalli
  • Baskaralingam Vaseeharan
  • Poonam Singh
  • Sanjeev Kumar Singh
چکیده

Enterococcus faecalis is a pathogenic Gram-positive bacterium, which mainly infects humans through urinary tract infections. SrtA is an essential enzyme for survival of E. faecalis, and inhibition of this particular enzyme will reduce the virulence of biofilm formation. It is proved to be associated with the microbial surface protein embedded signal transduction mechanism and promising as a suitable anti-microbial drug target for E. faecalis. The present work gives an inclusive description of SrtA isolated from E. faecalis through computational and experimental methodologies. For exploring the mechanism of SrtA and to screen potential leads against E. faecalis, we have generated three-dimensional models through homology modeling. The 3D model showed conformational stability over time, confirming the quality of the starting 3D model. Large scale 100 ns molecular dynamics simulations show the intramolecular changes occurring in SrtA, and multiple conformations of structure based screening elucidate potential leads against this pathogen. Experimental results showed that the screened compounds are active showing anti-microbial and anti-biofilm activity, as SrtA is known to play an important role in E. faecalis biofilm formation. Experimental results also suggest that SrtA specific screened compounds have better anti-biofilm activity than the available inhibitors. Therefore, we believe that development of these compounds would be an impetus to design the novel chief SrtA inhibitors against E. faecalis.

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عنوان ژورنال:
  • Molecular bioSystems

دوره 10 7  شماره 

صفحات  -

تاریخ انتشار 2014