title: Theoretical study of molecular determinants involved in signal binding to the TraR protein of Agrobacterium tumefaciens.
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.
authors.affiliation: School of Chemistry, The University of New South Wales, NSW, Australia.
authors.forename: Wai-Kean
authors.initials: WK
authors.lastname: Goh
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rice
authors.forename: Naresh
authors.initials: N
authors.lastname: Kumar
mesh_terms: D054742:Acyl-Butyrolactones / Q000737:chemistry / Q000378:metabolism*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D008024:Ligands; D008954:Models, Biological; D008958:Models, Molecular; D008962:Models, Theoretical; D011485:Protein Binding; D013379:Substrate Specificity
chemical_list: D054742:Acyl-Butyrolactones; D001426:Bacterial Proteins; D008024:Ligands; C080512:TraR protein, Agrobacterium tumefaciens