title: From dioxygen storing to dioxygen sensing with neuroglobins: an insight from molecular mechanics.
abstract: This work deals with two neuroglobins from phylogenetically distant organisms. Deriving from the acoelomorph Symsagittifera roscoffensis, SrNgb is functionally pentacoordinated, and is assumed to function as a reserve of dioxygen (O₂). Obtained from mice, mNgb is functionally hexacoordinated, and presumably triggers signals from sensing O₂. Here, it is investigated how these two globins are permeated by diatomic gases, SrNgb by O₂ and mNgb by CO. With protein atomic coordinates available from high-resolution X-ray diffraction analysis, O₂ and CO pathways were traced from molecular-dynamics simulations in H₂O solution, which makes no difference between the two gases, accelerated by applying an external randomly-oriented minimal force to the center of mass of the diatomic gas molecule. This allowed us to explore a statistically significant large number of trajectories. It emerged that CO leaves mNgb from preferentially peripheral gates located on the side of the heme propionate chains, whereas O₂ leaves SrNgb from the opposite side. This shows no analogy with either the functionally pentacoordinated, O₂-transporting, myoglobin (Mgb), or the hexacoordinated, O₂-sensing, cytoglobin, despite the same three-over-three typical α-helical globin folding. The sole analogy that could be observed was a preference for the shortest diatomic gas pathways with both SrNgb and Mgb. It is tempting to speculate that this fulfills the need of being quick in delivering O₂ to depleted organs.
authors.affiliation: Accademia Lucchese di Scienze, Lettere e Arti, Classe di Scienze, Palazzo Ducale, Lucca I-55100, Italy. francesco.pietra@accademialucchese.it
authors.forename: Francesco
authors.initials: F
authors.lastname: Pietra
mesh_terms: D000818:Animals; D001665:Binding Sites; D002248:Carbon Monoxide / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D005914:Globins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D056004:Molecular Dynamics Simulation; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D000078787:Neuroglobin; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D002248:Carbon Monoxide; D005914:Globins; D010100:Oxygen