In silico investigation and structural characterization of virulent factor and a metallo peptidase present in Helicobacter pylori strain J99.

VacA is a high-molecular weight multimeric pore-forming protein encoded by the chromosomal gene vacA of Helicobacter pylori J99 strian. It plays a significant role in the development of gastric cancer in human by inducing the formation of vacuoles. Genomics and proteomics features of an organism have provided a plethora of potential drug targets. The crystal structure of VacA is not available in any structural database; hence a 3D structure is very essential for structural studies and discovery of potential inhibitors against proteins. In this study 3D structure of VacA is modelled a by using Bhageerath: an energy based web enabled computer software suite. According to our study VacA steriochemical validation shows 91.7% residues are in allowed region of Ramachandran plot. Further validation was done by WHAT CHECK to provide evidence that the distribution of the main chain bond lengths and omega bond angles were within limits with Z-score 1.0 and error values are negligible. The modelled protein was submitted to Protein Model Database and can be downloaded with PMDID PM0077963. Further we found that metallo peptidase "M3" cleaves VacA and helps in import mechanism in mitochondria. Structure of metallo peptidase is also not available in any structural database so we modelled and validated its structure. With the help of docking studies we blocked the active site of metallo peptidase by ligand LA3 and 294 with binding energy -5.9 and -5.2 KJ/mol respectively, thus prevented import mechanism of VacA in mitochondria. The inhibitors identified from our study were LA3 and 294 ligands. The investigation concluded that these drugs could be used as the potential inhibitors against the damage of stomach and duodenum, which ultimately reduces the likelihood of ulcer as well as gastric cancer.