On Dioxygen and Substrate Access to Soluble Methane Monooxygenases: An all-Atom Molecular Dynamics Investigation in Water Solution.
In a preliminary exploration of the dummy model for diiron proteins, random-acceleration molecular dynamics (RAMD) revealed that a pure four-helix bundle structure, like hemerythrin, constitutes an efficient cage for dioxygen (O2), which can only leave from defined, albeit very broad, gates. However, this well ordered structure does not constitute an archetype on which to compare O2permeation of other diiron proteins, like the complex of soluble methane monooxygenase hydroxylase with the regulatory protein (sMMOH-MMOB). The reason is that with this complex, unlike hemerythrin, the four helices of the four-helix bundle are heavily bent, and RAMD showed that most traps for O2lie outside them. It was also observed that, in spite of a nearly identical van der Waals radius for O2and the natural substrate CH4, the latter behaves under RAMD as a bulkier molecule than O2, requiring a higher external force to be brought out of sMMOH-MMOB along trajectories of viable length. All that determined with sMMOH-MMOB multiple gates and multiple pathways to each of them through several binding pockets, for both O2and CH4. Of the two equally preferred pathways for O2, at right angle with one another, one proved to be in accordance with the Xe-atom mapping for sMMOH. In contrast, none of the pathways identified for CH4proved to be in accordance with such mapping, CH4looking for more open avenues instead.
Accademia Lucchese di Scienze, Lettere e Arti, Classe di Scienze, Palazzo Pretorio, IT-55100, Lucca.
Francesco
F
Pietra
D008697:Methane / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D010100:Oxygen / Q000737:chemistry* / Q000378:metabolism; D010105:Oxygenases / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013379:Substrate Specificity; D014867:Water / Q000737:chemistry
D014867:Water; D010105:Oxygenases; C021555:methane monooxygenase; D008697:Methane; D010100:Oxygen
Diiron proteins; Gas permeation of proteins; Hemerythrin; Multicomponent monooxygenases; Random acceleration molecular dynamics