Article Text
Abstract
Background N. gonorrhoeae, a major causative agent of STI, has acquired resistance to most of the commonly used drugs. Hence there is an urgent need to look for novel drug targets and new drugs to combat this disease. Although a large number of prokaryotic genomes have been sequenced, only a small percentage is completely annotated. Structure-function annotation of hypothetical proteins (HPs) can be exploited to identify novel drug targets.
Methods Various web tools were used under stringent condition to predict the function of different HPs and to identify novel drug targets based on their cellular localization, domains, motifs and by using STRING (http://string-db.org/) to identify their potential interactions with other proteins. To predict drug targets, essential genes were identified using DEG database and BLASTed against proteome of Homo sapiens to exclude homologous proteins.
Results Using bioinformatics tools, 206 HPs were analyzed for their subcellular localization. 140 HPs were predicted as cytoplasmic proteins and 10 as extracellular, Nine proteins in the outer membrane, seven as inner membrane whereas three in the periplasmic area. Using available tools, function to 32 HPs was assigned with high confidence; 11 proteins showed signal peptide whereas 21 proteins showed transmembrane helices. We predicted 19 proteins as putative enzymes crucial for the survival of Neisseria. These 19HPs were sub-classified as DNA modification system (5), transferases (3), hydrolase (3), FAD/NAD binding enzymes (5) and others (3). Other 12 HPs were characterized as transporter proteins including autotransporter (8), TonB dependent receptor (2), members of TAT pathway (1) and branched chain amino acid transporter (1). Two transporter proteins were predicted as adhesins and further classified as drug targets whereas five were predicted as vaccine candidates. We also predict five cytoplasmic and 4HPs localized in outer membrane as potential drug targets.
Conclusion These results are expected to be helpful in the development of improved therapeutics.
Disclosure No significant relationships.