title: Relating the diffusion of small ligands in human neuroglobin to its structural and mechanical properties.
abstract: Neuroglobin (Ngb), a recently discovered member of the globin family, is overexpressed in the brain tissues over oxygen deprivation. Unlike more classical globins, such as myoglobin and hemoglobin, it is characterized by a hexacoordinated heme, and its physiological role is still unknown, despite the numerous investigations made on the protein in recent years. Another important specific feature of human Ngb is the presence of two cysteine residues (Cys46 and Cys55), which are known to form an intramolecular disulfide bridge. Since previous work on human Ngb reported that its ligand binding properties could be controlled by the coordination state of the Fe(2+) atom (in the heme moiety) and the redox state of the thiol groups, we choose to develop a simulation approach combining coarse-grain Brownian dynamics and all-atom molecular dynamics and metadynamics. We have studied the diffusion of small ligands (CO, NO, and O(2)) in the globin internal cavity network for various states of human Ngb. Our results show how the structural and mechanical properties of the protein can be related to the ligand migration pathway, which can be extensively modified when changing the thiol's redox state and the iron's coordination state. We suggest that ligand binding is favored in the pentacoordinated species bearing an internal disulfide bridge.
authors.affiliation: Laboratoire de Biochimie Théorique, UPR 9080 CNRS Institut de Biologie Physico-Chimique, 13 rue Pierre et Marie Curie, 75005 Paris, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Bocahut
authors.forename: Sophie
authors.initials: S
authors.lastname: Bernad
authors.forename: Pierre
authors.initials: P
authors.lastname: Sebban
authors.forename: Sophie
authors.initials: S
authors.lastname: Sacquin-Mora
mesh_terms: D004058:Diffusion; D005914:Globins / Q000737:chemistry*; D006418:Heme / Q000737:chemistry; D006801:Humans; D008024:Ligands; D056004:Molecular Dynamics Simulation; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D000078787:Neuroglobin; D010084:Oxidation-Reduction; D017434:Protein Structure, Tertiary
chemical_list: D008024:Ligands; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D006418:Heme; D005914:Globins