5mjd

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== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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Neuroglobin (Ngb) is a globin expressed in the nervous system of humans and other organisms that is involved in the protection of the brain from ischemic damage. Despite considerable interest, however, the in vivo function of Ngb is still a conundrum. In this paper we report a number of kinetic experiments with O2 and NO that we have interpreted on the basis of the 3D structure of Ngb, now available for human and murine metNgb and murine NgbCO. The reaction of reduced deoxyNgb with O2 and NO is slow (t(1/2) approximately 2 s) and ligand concentration-independent, because exogenous ligand binding can only occur upon dissociation of the distal His-64, which is coordinated to the ferrous heme iron. By contrast, NgbO2 reacts very rapidly with NO, yielding metNgb and NO3- by means of a heme-bound peroxynitrite intermediate. Steady-state amperometric experiments show that Ngb is devoid of O2 reductase and NO reductase activities. To achieve this result, we have set up a protocol for efficient reduction of metNgb using a mixture of FMN and NADH under bright illumination. The results are discussed with reference to a global scheme inspired by the 3D structures of metNgb and NgbCO. Based on the ligand-linked conformational changes discovered by crystallography, the pathways of the reactions with O2 and NO provide a framework that may account for the involvement of Ngb in controlling the activation of a protective signaling mechanism.
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A combined biophysical approach was applied to map gas-docking sites within murine neuroglobin (Ngb), revealing snapshots of events that might govern activity and dynamics in this unique hexacoordinate globin, which is most likely to be involved in gas-sensing in the central nervous system and for which a precise mechanism of action remains to be elucidated. The application of UV-visible microspectroscopy in crystallo, solution X-ray absorption near-edge spectroscopy and X-ray diffraction experiments at 15-40 K provided the structural characterization of an Ngb photolytic intermediate by cryo-trapping and allowed direct observation of the relocation of carbon monoxide within the distal heme pocket after photodissociation. Moreover, X-ray diffraction at 100 K under a high pressure of dioxygen, a physiological ligand of Ngb, unravelled the existence of a storage site for O2 in Ngb which coincides with Xe-III, a previously described docking site for xenon or krypton. Notably, no other secondary sites were observed under our experimental conditions.
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Neuroglobin, nitric oxide, and oxygen: functional pathways and conformational changes.,Brunori M, Giuffre A, Nienhaus K, Nienhaus GU, Scandurra FM, Vallone B Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8483-8. doi:, 10.1073/pnas.0408766102. Epub 2005 Jun 2. PMID:15932948<ref>PMID:15932948</ref>
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Ligand pathways in neuroglobin revealed by low-temperature photodissociation and docking experiments.,Ardiccioni C, Arcovito A, Della Longa S, van der Linden P, Bourgeois D, Weik M, Montemiglio LC, Savino C, Avella G, Exertier C, Carpentier P, Prange T, Brunori M, Colloc'h N, Vallone B IUCrJ. 2019 Jul 10;6(Pt 5):832-842. doi: 10.1107/S2052252519008157. eCollection, 2019 Sep 1. PMID:31576217<ref>PMID:31576217</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

Revision as of 05:50, 10 October 2019

metNgb under oxygen at 80 bar

PDB ID 5mjd

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