title: Modeling of macromolecular proteins in prophenoloxidase cascade through experimental and computational approaches.
abstract: Prophenoloxidase (ProPO) cascade is a principal defense system in crustaceans, which consists of a variety of pattern recognition proteins (lipopolysaccharide and β-glucan-binding protein [β-GBP], β-GBP, and β-glucan recognition protein), proteases (serine protease), and protease inhibitors (α2-macroglobulin and pacifastin) to regulate the protection mechanism in crustaceans. In the prophneoloxidase pathway, the protein-protein interactions (PPIs) and other immune-related analyses still have not been reported. Moreover, the structural features of ProPO cascade proteins have not yet been reported, hence we constructed the three-dimensional structural features for all ProPO pathway proteins. Their PPIs were studied through an in silico approach. Laminarin has been identified as a triggering activator and it showed energetic binding with homology modeled β-GBP and activated the β-GBP, followed by the protein-protein complex formation leading to phenoloxidase synthesis. These findings provided a novel view of the ProPO mechanism and enhanced our knowledge of the innate immune system in crustaceans via computation. In conclusion, we propose a combined experimental and computational approach to analyze the mechanism of ProPO cascade proteins.
authors.affiliation: Crustacean Molecular Biology and Genomics Lab, Department of Animal Health and Management, Alagappa University, Karaikudi, India.|Bioinformatics & Biosignal Transduction, College of Bioscience, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Jeyachandran
authors.initials: J
authors.lastname: Sivakamavalli
authors.affiliation: Computer Aided Drug Designing and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi, India.|Department of Chemical Engineering, Konkuk University, Gwangjin-gu, Seoul, Korea.
authors.forename: Chandrabose
authors.initials: C
authors.lastname: Selvaraj
authors.affiliation: Computer Aided Drug Designing and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi, India.
authors.forename: Sanjeev Kumar
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Crustacean Molecular Biology and Genomics Lab, Department of Animal Health and Management, Alagappa University, Karaikudi, India.
authors.forename: Baskaralingam
authors.initials: B
authors.lastname: Vaseeharan
mesh_terms: D000818:Animals; D003386:Brachyura / Q000201:enzymology; D004156:Catechol Oxidase / Q000737:chemistry / Q000378:metabolism*; D004792:Enzyme Precursors / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D047071:beta-Glucans / Q000378:metabolism
chemical_list: D004792:Enzyme Precursors; D008024:Ligands; D047071:beta-Glucans; C038451:pro-phenoloxidase; D004156:Catechol Oxidase
keywords: PO activity; pattern recognition proteins; phenoloxidase; protein-protein interactions