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.

On the Permeation by Dioxygen of Urate Oxidase from Aspergillus flavus in Complex with Xanthine Anion: Dioxygen Pathways and a Portrait of the Enzyme Cavities from Molecular Dynamics Simulations in Water Solution

“…This is not a characteristic of all protein–gas systems that I have investigated. Out of these, referred to at section above, it was only with myoglobin , cytoglobin , Symsagittifera roscoffiensis neuroglobin , and heme oxygenase OH‐1 , that the shortest pathway between the active center and the bulk solvent was preferred. For these, we speculated that rapid supply of O 2 along the shortest pathway reflects the urgent cellular need of O 2 , which led to the evolution of ad hoc O 2 carriers, sensors, and enzymes.…”

“…In a similar vein, we have also investigated by MD the permeation by O 2 of other proteins, including O 2 ‐sensors , oxygenases , oxidases , oxidoreductases , and singlet dioxygen generators . None of these proteins has the special features of UOX, with the active center at the interface between two subunits, thus likely requiring the intact homotetramer for functioning.…”

Gates and Binding Pockets for Nitric Oxide with Cytochrome c′, According to Molecular Dynamics

“…Present study of AXCPÀNO complexes has been carried out along RAMD simulations [13], as in previous examples of permeation of proteins by biologically relevant gases, concerning myoglobin [14], H-NOX [15], lipoxygenases [16], MauG [17], cytoglobin [18], heme oxygenase [19], and neuroglobins [20]. With RAMD simulations [13], a randomly oriented tiny force is applied to the center of mass of the ligand.…”

Significantly Enhanced Heme Retention Ability of Myoglobin Engineered to Mimic the Third Covalent Linkage by Nonaxial Histidine to Heme (Vinyl) in Synechocystis Hemoglobin

“…Many of them displayed novel characteristics not seen in the classical globins like myoglobin (Mb). A literature search revealed that folding and stability of Hbs were not investigated for diverse globins (15,16). Most of the contributions relate to Mb and human Hb (17)(18)(19)(20)(21)(22)(23).…”