Genome-wide survey and phylogeny of S-Ribosylhomocysteinase (LuxS) enzyme in bacterial genomes

Rajas M. Rao, Shaik Naseer Pasha, Ramanathan Sowdhamini

The study of survival and communication of pathogenic bacteria is important to combat diseases caused by such micro-organisms. Bacterial cells communicate with each other using a density-dependent cell-cell communication process called Quorum Sensing (QS). LuxS protein is an important member of interspecies quorum-sensing system, involved in the biosynthesis of Autoinducer-2 (AI-2), and has been identified as a drug target. Despite the above mentioned significance, their evolution has not been fully studied, particularly from a structural perspective. Search for LuxS in the non-redundant database of protein sequences yielded 3106 sequences. Phylogenetic analysis of these sequences revealed grouping of sequences into five distinct clusters belonging to different phyla and according to their habitat. A majority of the neighbouring genes of LuxS have been found to be hypothetical proteins. However, gene synteny analyses in different bacterial genomes reveal the presence of few interesting gene neighbours. Moreover, LuxS gene was found to be a component of an operon in only six out of 36 genomes. Analysis of conserved motifs in representative LuxS sequences of different clusters revealed the presence of conserved motifs common to sequences of all the clusters as well as motifs unique to each cluster. Homology modelling of LuxS protein sequences of each cluster revealed few structural features unique to protein of each cluster. Analyses of surface electrostatic potentials of the homology models of each cluster showed the interactions that are common to all the clusters, as well as cluster-specific potentials and therefore interacting partners, which may be unique to each cluster. LuxS protein evolved early during the course of bacterial evolution, but has diverged into five subtypes. Analysis of sequence motifs and homology models of representative members reveal cluster-specific structural properties of LuxS. Further, it is also shown that LuxS protein may be involved in various protein-protein or protein-RNA interactions, which may regulate the activity of LuxS proteins in bacteria.