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Molecular modeling and active site analysis of SdiA homolog, a putative quorum sensor for Salmonella typhimurium pathogenecity reveals specific binding patterns of AHL transcriptional regulators

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Abstract

Salmonella typhimurium is a Gram-negative bacterium responsible for human diseases including gastroenteritis and typhoid fever and its quorum sensing system is currently being intensively researched. Molecular modeling and binding site analysis of SdiA homolog, a putative quorum sensor of the LuxR family and responsible for S. typhimurium pathogenecity revealed a high structural homology of their active site with three other LuxR family proteins LasR from Pseudomonas aeruginosa, TraR from Agrobacterium tumifaciens and CviR from Chromobacterium violaceum. The results show that all the LuxR family proteins harbor three conserved amino acids Tryptophan (W67) and Aspartic acid (D80) for formation of hydrogen bridges and Tyrosine (Y71) for the hydrophobic interactions (corresponding to their position in S. typhimurium SdiA) with acyl homoserine lactones (AHL) –dependent transcriptional regulators. However, in addition to the above conserved residues, Arginine (R60) also plays an important role in S. typhimurium SdiA binding with its AHL auto inducers and the complex is found to be stronger because of the interactions between nitrogen atoms of Arginine with the carbonyl oxygen in the lactone ring of AHL. The specific binding patterns would be helpful in guiding both enzymatic studies as well as design of specific inhibitors to overcome S. typhimurium pathogenecity.

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Authors and Affiliations

  1. Department of Bioinformatics, Vivekanandha College of Arts and Sciences for Women, Tiruchengode, 637 205, India

    Shanmugam Gnanendra

  2. Department of Bioinformatics, VMKV Engineering College, Vinayaka Missions University, Salem, 636 308, India

    Shanmugam Anusuya

  3. Department of Bioinformatics, Bharathiar University, Coimbatore, 641 046, India

    Shanmugam Gnanendra, Shanmugam Anusuya & Jeyakumar Natarajan

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  1. Shanmugam Gnanendra
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  2. Shanmugam Anusuya
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  3. Jeyakumar Natarajan
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Correspondence to Shanmugam Gnanendra, Shanmugam Anusuya or Jeyakumar Natarajan.

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Gnanendra, S., Anusuya, S. & Natarajan, J. Molecular modeling and active site analysis of SdiA homolog, a putative quorum sensor for Salmonella typhimurium pathogenecity reveals specific binding patterns of AHL transcriptional regulators. J Mol Model 18, 4709–4719 (2012). https://doi.org/10.1007/s00894-012-1469-1

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