Elucidation of the hetero-dimeric binding activity of LasR and RhlR proteins with the promoter DNA and the role of a specific Phe residue during the biosynthesis of HCN synthase from opportunistic pathogen Pseudomonas aeruginosa

Abstract

Pseudomonas aeruginosa is an opportunistic human pathogen. It causes secondary infections in patients suffering from cancer and other immunological disorders. The pathogenicity of the organism is dependent on the ability of the organism to code for hydrogen cyanide (HCN), the synthesis of which is mediated by HCN synthase enzyme. HCN synthase is encoded by hcnABC operon. The transcription of the operon is controlled by a complex interplay between the proteins LasR and RhlR. Till date, there is no report that deals with the binding interactions of the RhlR-LasR heterodimer with the promoter DNA region of the hcnABC operon. We, for the first time, tried to analyse the binding modes of the RhlR-LasR heterodimer with the promoter DNA regions. From our work, we could predict the importance of a specific amino acid residue Phe214 from RhlR which might be considered to have the desired specificity to bind to the promoter DNA. Therefore, the amino acid Phe214 may be targeted to develop suitable ligands to eradicate the spread of secondary infections by Pseudomonas aeruginosa.

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Acknowledgements

The authors would like to thank ICMR (Grant no. BIC/12(02)/2014) for financial support. The support from the DBT-sponsored Bioinformatics Infrastructure Facility Centre of Kalyani University, DST-FIST-II, UGC-SAP-DRSII and University of Kalyani is also acknowledged.

Funding

The authors would like to thank ICMR (Grant no. BIC/12(02)/2014) for financial support. The support from the DBT-sponsored Bioinformatics Infrastructure Facility Centre of Kalyani University, DST-FIST-II, UGC-SAP-DRSII and University of Kalyani is also acknowledged.

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NC and AB designed the work. NC performed the work. AB conceptualized the work. Both the authors wrote the manuscript.

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Correspondence to Angshuman Bagchi.

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Chowdhury, N., Bagchi, A. Elucidation of the hetero-dimeric binding activity of LasR and RhlR proteins with the promoter DNA and the role of a specific Phe residue during the biosynthesis of HCN synthase from opportunistic pathogen Pseudomonas aeruginosa. J Mol Model 27, 76 (2021). https://doi.org/10.1007/s00894-021-04701-8

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Keywords

  • LasR-RhlR heterodimer
  • DNA-protein interactions
  • Heterodimer formation
  • Molecular dynamics simulations
  • Molecular docking