title: Binding pockets and permeation channels for dioxygen through cofactorless 3-hydroxy-2-methylquinolin-4-one 2,4-dioxygenase in association with its natural substrate, 3-hydroxy-2-methylquinolin-4(1H)-one. A perspective from molecular dynamics simulations.
abstract: This work describes an investigation of pathways and binging pockets (BPs) for dioxygen (O2 ) through the cofactorless oxygenase 3-hydroxy-2-methylquinolin-4-one 2,4-dioxygenase in complex with its natural substrate, 3-hydroxy-2-methylquinolin-4(1H)-one, in aqueous solution. The investigation tool was random-acceleration molecular dynamics (RAMD), whereby a tiny, randomly oriented external force is applied to O2 in order to accelerate its movements. In doing that, care was taken that the external force only continues, if O2 moves along a direction for a given period of time, otherwise the force changed direction randomly. Gates for expulsion of O2 from the protein, which can also be taken as gates for O2 uptake, were found throughout almost the whole external surface of the protein, alongside a variety of BPs for O2 . The most exploited gates and BPs were not found to correspond to the single gate and BP proposed previously from the examination of the static model from X-ray diffraction analysis of this system. Therefore, experimental investigations of this system that go beyond the static model are urgently needed.
authors.affiliation: Accademia Lucchese di Scienze, Lettere e Arti, Classe di Scienze, Palazzo Ducale, Lucca I-55100, (phone and fax: +39 0583 417336). francesco.pietra@accademialucchese.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Pietra
mesh_terms: D001688:Biological Products / Q000737:chemistry* / Q000378:metabolism; D049308:Dioxygenases / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D010100:Oxygen / Q000737:chemistry* / Q000378:metabolism; D015363:Quinolones / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001688:Biological Products; D015363:Quinolones; D049308:Dioxygenases; D010100:Oxygen
keywords: 3-Hydroxy-2-methylquinolin-4-one 2,4-dioxygenase; Arthrobacter nitroguajacolicus enzymes; Dioxygen permeation of proteins; Proteins; Random-acceleration molecular dynamics (RAMD); α/β-Hydrolase fold enzymes