Substrate specificities in Salmonella typhi outer membrane protease (PgtE) from Omptin family – An in silico proteomic approach

Abstract

Salmonella typhi are Gram-negative pathogen causes severe systemic infections like typhoid fever and gastrointestinal disease in humans. PgtE belongs to Omptin family, plays a central role at the host-pathogen interface. In the present study, S. typhi PgtE sequence retrieved and cleavage sites were predicted. Owing to the non-existence of crystal structure of S. typhi PgtE, theoretical 3D modeled structures were predicted with I-TASSER server, which helps to understand the protease inhibitory mechanism. Molecular interaction studies with known protease inhibitors were revealed that aspartic protease inhibitor Indinavir has the best interaction with S. typhi PgtE. From the metal ion docking studies, Mg2+ has better interaction, while compared to Zn2+ and Cu2+ ions. The multiple pathogen sequence alignment of Omptin proteases family shows that, interacting residues were conserved among the Omptins. These results will provide new knowledge for the development of novel therapeutic strategies against S. typhi PgtE and Omptin family proteases. Keywords: Aspartic protease, Omptin, Outer membrane proteases and catalytic activity