RELATIVE STRUCTURAL ANALYSIS OF LytTR DOMAIN OF AgrA PROTEIN INVOLVED IN BACTERIAL QUORUM SENSING

Resistance to antimicrobials by pathogenic bacteria is a global menace. An attractive pathway to resolve this problem of resistance may be achieved by targeting the bacterial quorum sensing (QS) process. Fighting bacterial infections by interfering with their command language and disrupting virulence expression could serve as a viable alternative. One of the current strategies is to attenuate virulence gene expression of agr quorum sensing system of some Gram-positive bacteria through inhibition of AgrA_ P2/P3 interaction. Tertiary structures of AgrA proteins of some pathogenic bacteria like Listeria monocytogenes, Chlamydia trachomatis, Enterococcus faecalis, Streptococcus pyogenes and Macrococcus canis showing antimicrobial resistance are not yet available in structural databases like PDB. These proteins play a key role in AgrA quorum sensing. 3D structures of these proteins are essential to determine most of their functions, and for the development of agents that can be explored as therapeutic agents. In order to derive structures of these AgrA proteins, homology modeling approach was employed. The modeled proteins were validated by several methods, and the physico-chemical properties of these refined protein structures were predicted using in-silico methods. The compositional and structural differences of the LytTR domain of AgrA proteins between the pathogenic and non-pathogenic bacteria were analyzed in our study. We have also identified the cleft and cavities in these structures and have explored the potential binding sites. The structural features of these sites have also been studied to have a better understanding of screening/designing inhibitors.