title: A possible mechanism for redox control of human neuroglobin activity.
abstract: Neuroglobin (Ngb) promotes neuron survival under hypoxic/ischemic conditions. In vivo and in vitro assays provide evidence for redox-regulated functioning of Ngb. On the basis of X-ray crystal structures and our MD simulations, a mechanism for redox control of human Ngb (hNgb) activity via the influence of the CD loop on the active site is proposed. We provide evidence that the CD loop undergoes a strand-to-helix transition when the external environment becomes sufficiently oxidizing, and that this CD loop conformational transition causes critical restructuring of the active site. We postulate that the strand-to-helix mechanics of the CD loop allows hNgb to utilize the lability of Cys46/Cys55 disulfide bonding and of the Tyr44/His64/heme propionate interaction network for redox-controlled functioning of hNgb.
authors.affiliation: Department of Chemistry and Biochemistry, Florida International University , Miami, Florida 33199, United States.
authors.forename: Alexander N
authors.initials: AN
authors.lastname: Morozov
authors.forename: James P
authors.initials: JP
authors.lastname: Roach
authors.forename: Margarita
authors.initials: M
authors.lastname: Kotzer
authors.forename: David C
authors.initials: DC
authors.lastname: Chatfield
mesh_terms: D004220:Disulfides / Q000737:chemistry; D005914:Globins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D056004:Molecular Dynamics Simulation; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D000078787:Neuroglobin; D010084:Oxidation-Reduction; D017433:Protein Structure, Secondary
chemical_list: D004220:Disulfides; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D005914:Globins