In silico approach on sequential and structural variability in oryzacystatin and its interaction with cysteine protease enzymes of insect

Abstract

Phytoprotease inhibitors (PI) are important defence compounds produced by plants against microbes and insect herbivory. Oryzacystatins (OCs) are a group of protease inhibitors from Oryza sativa L. that are specific against cysteine protease enzymes. This study revealed the evolutionary relationship of eleven different oryzacystatins from rice and their interaction with cysteine protease enzymes from brown planthopper (BPH) and striped stem borer (SSB). Three-dimensional structure of eleven different oryzacystatins and six cysteine protease enzymes were homologically modelled, and their interaction was analysed to explore the sequence heterogeneity, structural variability and functional significance. OC XI and OC V showed higher docking score and hydrogen bond interaction with all the six tested cysteine protease enzymes. N terminal glycine residue, central conserved QVVXG, C terminal AVVXXXPW regions are involved in interacting with the active site residue of protease enzymes. Substitution of N terminal glycine by any other residue in OC VI significantly reduced the interaction efficiency with cysteine proteases. In OC XI, glutamine in the fourth position of QVVXG showed higher interaction efficiency with all cysteine proteases than serine at the fourth amino acid position. N terminal glycine plays a vital role in OC XI for interacting with active sites of cysteine protease enzymes whereas, in the OC V central conserved region QVVSG and C terminal PW region plays a major part in the interaction. However, either N terminal or C terminal region along with the central conserved region of oryzacystatin is involved in mediating an efficient interaction with the active site residues of cysteine proteases. Molecular dynamic (MD) simulation study revealed the stability of the OC X1 - cathepsin O2 like and OC V - cathepsin F like complexes during a simulation for 20 ns. Insilico results of the present study predict the potential of oryzacystatins interaction with cysteine protease enzymes of insects.

Keywords: Cysteine protease enzyme; Molecular docking; Molecular dynamic simulation; Oryza sativa L. Poaceae; Oryzacystatin; Protein-protein interaction.