Molecular docking analysis of juglone with parvulin-type PPiase PrsA from .

is an opportunistic pathogen that causes variety of infections range from mild skin diseases to life-threatening sepsis. It is also notorious for acquiring resistance to numerous antibiotics. Parvulin-type peptidyl-prolyl cis-trans isomerase (PPiase) domain containing PrsA protein is considered as an essential folding factor for secreted proteins of Gram-positive bacteria. Therefore, it is considered as a potential target for anti-staphylococcal drug discovery. Juglone, plant-derived 1,4-naphthoquinone, shows confirmed antitumor and antibacterial activities. Destruction of bacterial biofilm, inhibition of enzyme expression, degradation of nucleic acids, and other pathways are likely the major possible mechanisms for inactivation by juglone. Selective inhibition of parvulin type PPiase by juglone has been proven biochemically. However, detail structural information of parvulin-juglone interaction and mechanism of enzymatic inhibition till unexplored. Past hypothesis on inactivation of parvulin type PPiase due to covalent attachment of juglone molecules to its cysteine residues is not acceptable for the PrsA parvulin domain as that lacks cysteine. Docking studies showed that juglone binds to the active site residues of PrsA parvulin domain involved in enzymatic reaction. Active site conserved histidine residue of parvulin may be involved in juglone interaction as it was found to be the common interactive residue in majority of docking complexes. Data shows Juglone possibly inhibits parvulin type PPiase through competitive inhibition mechanism. Subtle differences of juglone interactions with other orthologous parvulin domains will help to develop semisynthetic drug with higher specificity against .