title: Homology modeling, docking, molecular dynamics simulation, and structural analyses of coxsakievirus B3 2A protease: an enzyme involved in the pathogenesis of inflammatory myocarditis.
abstract: 2A protease of the pathogenic coxsackievirus B3 is key to the pathogenesis of inflammatory myocarditis and, therefore, an attractive drug target. However lack of a crystal structure impedes design of inhibitors. Here we predict 3D structure of CVB3 2A(pro) based on sequence comparison and homology modeling with human rhinovirus 2A(pro). The two enzymes are remarkably similar in their core regions. However they have different conformations at the N-terminal. A large number of N-terminal hydrophobic residues reduce the thermal stability of CVB3 2A(pro), as we confirmed by fluorescence, western blot and turbidity measurement. Molecular dynamic simulation revealed that elevated temperature induces protein motion that results in frequent movement of the N-terminal coil. This may therefore induce successive active site changes and thus play an important role in destabilization of CVB3 2A(pro) structure.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Amir Hossein
authors.initials: AH
authors.lastname: Maghsoudi
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
authors.forename: Hamid
authors.initials: H
authors.lastname: Hadi-Alijanvand
authors.forename: Mitra
authors.initials: M
authors.lastname: Esfandiarei
authors.forename: Marjan
authors.initials: M
authors.lastname: Sabbaghian
authors.forename: Zahra
authors.initials: Z
authors.lastname: Zakeri
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Shaerzadeh
authors.forename: Shervin
authors.initials: S
authors.lastname: Abtahi
authors.forename: Nader
authors.initials: N
authors.lastname: Maghsoudi
mesh_terms: D020134:Catalytic Domain; D003546:Cysteine Endopeptidases / Q000737:chemistry; D029822:Enterovirus B, Human; D006367:HeLa Cells; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000201:enzymology*; D056004:Molecular Dynamics Simulation; D009205:Myocarditis / Q000150:complications / Q000201:enzymology* / Q000209:etiology*; D011489:Protein Denaturation; D017433:Protein Structure, Secondary; D040681:Structural Homology, Protein; D013696:Temperature; D014364:Tryptophan / Q000737:chemistry; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: C500427:3A protein, coxsackievirus B; D014764:Viral Proteins; D014364:Tryptophan; D003546:Cysteine Endopeptidases; C057400:picornain 2A, Picornavirus