Abstract
N-acylated homoserine lactone (AHL) mediated cell-cell communication in bacteria is dependent on the recognition of the cognate signal by its receptor. This interaction allows the receptor-ligand complex to act as a transcriptional activator, controlling the expression of a range of bacterial phenotypes, including virulence factor expression and biofilm formation. One approach to determine the key features of signal-binding is to model the intermolecular interactions between the receptor and ligand using computational-based modeling software (LigandFit). In this communication, we have modeled the crystal structure of the AHL receptor protein TraR and its AHL signal N-(3-oxooctanoyl)-homoserine lactone from Agrobacterium tumefaciens and compared it to the previously reported antagonist behaviour of a number of AHL analogues, in an attempt to determine structural constraints for ligand binding. We conclude that (i) a common conformation of the AHL in the hydrophobic and hydrophilic region exists for ligand-binding, (ii) a tail chain length threshold of 8 carbons is most favourable for ligand-binding affinity, (iii) the positive correlation in the docking studies could be used a virtual screening tool.
Highlights
Traditional treatment of bacterial related diseases is based upon chemicals that kill or inhibit the growth of the bacteria
The crystal structure of the TraR protein complexed with its autoinducer N-(3oxooctanoyl)-L-homoserine lactone (HSL), (3-oxooctanoyl-HSL) (Figure 2), and target DNA was retrieved from the Protein Data Bank
When the biological activities were compared to the two scoring functions, a similar rank order was observed for six ligands that exhibited competitive antagonist behaviour: 3-oxoheptanoyl-HSL (4); 3-oxoundecanoyl-HSL (6); 3-oxododecanoyl-HSL (7); heptanoyl-HSL (11); octanoyl-HSL (12); and 3-hydroxynonanoyl-HSL (24)
Summary
Traditional treatment of bacterial related diseases is based upon chemicals that kill or inhibit the growth of the bacteria. These drugs work against microorganisms by breaching their cell walls, disrupting metabolism, or inhibiting macromolecule synthesis. It is well understood that some pathogenic bacteria rely on the secretion and detection of small diffusible cues/signals, to control the expression of virulence [1,2,3]. One such quorum sensing (QS) system, found in Gram-negative bacteria, is the N-acylated homoserine lactone (AHL) system, which has been shown to control phenotypes such as virulence factor production and biofilm formation [4,5]
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