Structural Modeling of Leukotoxin a Secreted by Aggregatibacter Actinomycetemcomitans As a Target for Biopharmaceutical Applications



Pourhajibagher M¹ ; Gharesi S² ; Ghorbanzadeh R³ Show Affiliations
Source: Der Pharma Chemica Published:2015

Abstract

Aggregatibacter actinomycetemcomitans is a major putative periodontopathic microorganism that produces a repeats-in-toxin (RTX) leukotoxin (LtxA) that selectively kills human immune cells. systemically administered antibiotics are recommended for removal of this bacterium frominfected periodontium. But recently, the use of conventional antibiotics is limited due to theemergence of antibiotic resistance among A. actinomycetemcomitans isolates. consequently, it is imperative that new drugs used for the treatment of A. actinomycetemcomitans infections. In this study, using bioinformatic tools and computer simulation molecular modelling, we introduced the ltxa protein of A. actinomycetemcomitans as a new drug target for treatment infections caused by A. actinomycetemcomitans. Hydropathy analysis of ltxa protein (114194.6 dalton; 1050amino acids) predicts four domains: N-terminal region, the central region, the repeat region and the C-terminal region. Protein interaction network have shown the association among LtxA with ten functional partners. Our findings suggest that ltxa is a stable protein that was concentrated outside of the cells. Computational approach has facilitated the search for potential drug targets. More detailed analysis of biochemical pathways of ltxa set high hopes and provideinsight into the development of new antibiotics for appropriate treatments of A. actinomycetemcomitans infections.