title: Coupling of the heme and an internal disulfide bond in human neuroglobin.
abstract: Neuroglobin displays a hexacoordination His-Fe-His in the absence of external ligands such as oxygen. The observed oxygen affinity therefore depends on the binding rates of both oxygen and the competing distal histidine. Furthermore, the binding properties depend on the presence of an internal disulfide bond. In the case of human neuroglobin, cysteines at positions CD7 and D5 are sufficiently close to form an internal disulfide bond. For cytoglobin, the cysteine residues at positions A7 and GH4 may also form a disulfide bond. Mass spectrometry, ligand binding, and thiol accessibility studies were used to study the role influence of these disulfide bonds. Mutation of specific cysteines, or reduction to break the S-S bond, led to a large decrease in the observed oxygen affinity of human neuroglobin, mainly due to a decrease in the histidine dissociation rate. This suggests a novel mechanism for the oxygen binding; reduction of the disulfide bond would provoke the release of oxygen.
authors.affiliation: Inserm U473, 84 rue du General Leclerc, 94276 Le Kremlin-Bicêtre, Cedex France.
authors.forename: Djemel
authors.initials: D
authors.lastname: Hamdane
authors.forename: Laurent
authors.initials: L
authors.lastname: Kiger
authors.forename: Sylvia
authors.initials: S
authors.lastname: Dewilde
authors.forename: Brian N
authors.initials: BN
authors.lastname: Green
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pesce
authors.forename: Julien
authors.initials: J
authors.lastname: Uzan
authors.forename: Thorsten
authors.initials: T
authors.lastname: Burmester
authors.forename: Thomas
authors.initials: T
authors.lastname: Hankeln
authors.forename: Martino
authors.initials: M
authors.lastname: Bolognesi
authors.forename: Luc
authors.initials: L
authors.lastname: Moens
authors.forename: Michael C
authors.initials: MC
authors.lastname: Marden
mesh_terms: D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry*; D005914:Globins / Q000737:chemistry*; D006418:Heme / Q000737:chemistry*; D006801:Humans; D013058:Mass Spectrometry; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D000078787:Neuroglobin; D010100:Oxygen / Q000378:metabolism
chemical_list: D004220:Disulfides; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D006418:Heme; D005914:Globins; D003545:Cysteine; D010100:Oxygen