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.
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.
Department of Bioinformatics, Vivekanandha College of Arts and Sciences for Women, Tiruchengode 637205, India. gnani.science@gmail.com
Shanmugam
S
Gnanendra
Shanmugam
S
Anusuya
Jeyakumar
J
Natarajan
D054742:Acyl-Butyrolactones / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000596:Amino Acids; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020134:Catalytic Domain; D017124:Conserved Sequence; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D053038:Quorum Sensing; D012097:Repressor Proteins / Q000737:chemistry; D015203:Reproducibility of Results; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity*; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D040681:Structural Homology, Protein; D013816:Thermodynamics; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014774:Virulence / Q000235:genetics
D054742:Acyl-Butyrolactones; D000596:Amino Acids; D001426:Bacterial Proteins; D012097:Repressor Proteins; C097686:SdiA protein, bacteria; D015534:Trans-Activators; C064778:LuxR autoinducer binding proteins