Theoretical Study of Molecular Determinants Involved in Signal Binding to the TraR Protein of Agrobacterium tumefaciens 英文参考文献.docVIP

Molecules 2005, 10, 1263–1271 molecules ISSN 1420-3049 Theoretical Study of Molecular Determinants Involved in Signal Binding to the TraR Protein of Agrobacterium tumefaciens Wai-Kean Goh 1, Scott A. Rice 2 and Naresh Kumar 1,* 1 School of Chemistry and 2 The Centre for Marine Biofouling and Bio-Innovation, The University of New South Wales, NSW 2052, Australia. Tel. +(612)-9385-4698 * Author to whom correspondence should be addressed; e-mail: n.kumar@.au Received: 1 December 2004 / Accepted: 20 April 2005/ Published: 31 October 2005 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. Keywords: Quorum sensing, TraR, N-acyl homoserine lactone, Molecular modeling, AHL receptor binding.