| Structural highlights
5mjc is a 1 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , |
| Related: | 1oj6, 3gkt, 4o4t |
| Gene: | Ngb (LK3 transgenic mice) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[NGB_MOUSE] Involved in oxygen transport in the brain. Hexacoordinate globin, displaying competitive binding of oxygen or the distal His residue to the iron atom. Not capable of penetrating cell membranes. The deoxygenated form exhibits nitrite reductase activity inhibiting cellular respiration via NO-binding to cytochrome c oxidase. Involved in neuroprotection during oxidative stress. May exert its anti-apoptotic activity by acting to reset the trigger level of mitochondrial cytochrome c release necessary to commit the cells to apoptosis.[1] [2]
Publication Abstract from PubMed
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.
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[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Couture M, Burmester T, Hankeln T, Rousseau DL. The heme environment of mouse neuroglobin. Evidence for the presence of two conformations of the heme pocket. J Biol Chem. 2001 Sep 28;276(39):36377-82. Epub 2001 Jul 25. PMID:11473111 doi:http://dx.doi.org/10.1074/jbc.M103907200
- ↑ Dewilde S, Kiger L, Burmester T, Hankeln T, Baudin-Creuza V, Aerts T, Marden MC, Caubergs R, Moens L. Biochemical characterization and ligand binding properties of neuroglobin, a novel member of the globin family. J Biol Chem. 2001 Oct 19;276(42):38949-55. Epub 2001 Jul 25. PMID:11473128 doi:http://dx.doi.org/10.1074/jbc.M106438200
- ↑ Brunori M, Giuffre A, Nienhaus K, Nienhaus GU, Scandurra FM, Vallone B. Neuroglobin, nitric oxide, and oxygen: functional pathways and conformational changes. 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 doi:http://dx.doi.org/10.1073/pnas.0408766102
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