title: Crucial roles of Glu60 in human neuroglobin as a guanine nucleotide dissociation inhibitor and neuroprotective agent.
abstract: Mammalian neuroglobin (Ngb) protects neuronal cells under conditions of oxidative stress. We previously showed that human Ngb acts as a guanine nucleotide dissociation inhibitor (GDI) for the α-subunits of heterotrimeric Gi/o proteins and inhibits reductions in cAMP concentration, leading to protection against cell death. In the present study, we created human E60Q Ngb mutant and clarified that Glu60 of human Ngb is a crucial residue for its GDI and neuroprotective activities. Moreover, we investigated structural and functional properties of several human Ngb mutants and demonstrated that the neuroprotective effect of human Ngb is due to its GDI activity and not due to its scavenging activity against reactive oxygen species.
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro-ku, Tokyo, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro-ku, Tokyo, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, Meguro-ku, Tokyo, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Wakasugi
mesh_terms: D000595:Amino Acid Sequence; D002454:Cell Differentiation; D002460:Cell Line; D005914:Globins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018698:Glutamic Acid; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000078787:Neuroglobin; D009474:Neurons / Q000166:cytology
chemical_list: D020730:Guanine Nucleotide Dissociation Inhibitors; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D018698:Glutamic Acid; D005914:Globins