title: Reversible hexa- to penta-coordination of the heme Fe atom modulates ligand binding properties of neuroglobin and cytoglobin.
abstract: Neuroglobin (Ngb) and cytoglobin (Cygb) are two recently discovered intracellular members of the vertebrate hemoglobin (Hb) family. Ngb, predominantly expressed in nerve cells, is of ancient evolutionary origin and is homologous to nerve-globins of invertebrates. Cygb, present in many different tissues, shares common ancestry with myoglobin (Mb) and can be traced to early vertebrate evolution. Ngb is held to facilitate O2 diffusion to the mitochondria and to protect neuronal cells from hypoxic-ischemic insults, may be an oxidative stress-responsive sensor protein for signal transduction, and may carry out enzymatic activities, such as NO/O2 scavenging. Cygb is linked to collagen synthesis, may provide O2 for enzymatic reactions, and may be involved in a ROS(NO)-signaling pathway(s). Ngb and Cgb display the classical three-over-three alpha-helical fold of Hb and Mb, and are endowed with a hexa-coordinate heme-Fe atom, in their ferrous and ferric forms, having the heme distal HisE7 residue as the endogenous ligand. Reversible hexa- to penta-coordination of the heme Fe atom modulates ligand binding properties of Ngb and Cygb. Moreover, Ngb and Cygb display a tunnel/cavity system within the protein matrix held to facilitate ligand channeling to/from the heme, multiple ligand copies storage, multi-ligand reactions, and conformational transitions supporting ligand binding.
authors.affiliation: Department of Physics-INFM and Center for Excellence in Biomedical Research, University of Genova, Via Dodecaneso 33, I-16146 Genova, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pesce
authors.forename: Daniele
authors.initials: D
authors.lastname: De Sanctis
authors.forename: Marco
authors.initials: M
authors.lastname: Nardini
authors.forename: Sylvia
authors.initials: S
authors.lastname: Dewilde
authors.forename: Luc
authors.initials: L
authors.lastname: Moens
authors.forename: Thomas
authors.initials: T
authors.lastname: Hankeln
authors.forename: Thorsten
authors.initials: T
authors.lastname: Burmester
authors.forename: Paolo
authors.initials: P
authors.lastname: Ascenzi
authors.forename: Martino
authors.initials: M
authors.lastname: Bolognesi
mesh_terms: D000818:Animals; D000078842:Cytoglobin; D005914:Globins / Q000378:metabolism*; D006418:Heme / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000078787:Neuroglobin; D009687:Nuclear Proteins / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: C000627265:CYGB protein, human; C000627267:Cygb protein, mouse; D000078842:Cytoglobin; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D009687:Nuclear Proteins; D006418:Heme; D005914:Globins; D007501:Iron