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Title: Structural dynamics of Neuroglobin: photoreduction and phodissociation intermediates
Tutor: Vallone, Beatrice
Issue Date: 9-Jan-2011
Abstract: Neuroglobin (Ngb) is a member of the globin family expressed in the vertebrate brain and retina; it is involved in brain protection, especially after ischemia, but its mechanism of action remains elusive. The structural characterization of Ngb in its unbound and CO bound states has revealed the presence of a very large hydrophobic cavity and a wide heme sliding to allow gaseous molecule binding (1,2). These features are most likely connected with the activity of Ngb, that could consist of radical scavenging, namely NO, relying on the presence internal docking sites to enhance availability of gaseous ligands at the active site (3,4), during pathological or physiological conditions. We have been interested to provide a description of ligand pathways within the protein matrix and their role in its function. We have investigated the Ngb protein matrix with different tecniques: UV-Vis Microspectrophotometry on crystal (off-line and on-line), X-Ray Diffraction both at low and room and X-ray Absorption Spectroscopy in solution and on a single crystal. From our data we have found gas molecule (CO photolized and dioxygen)in three different sites and we hypothesize a possible distal ligand pathway toward or from the heme-ironduring which the following sites are occuoied: i) the XeIII binding site ii) the water 9 site and the iii) distal site of the heme, from which eventually binding is achieved.References 1. Vallone B, Nienhaus K, Brunori M, Nienhaus G.U. (2004) Proteins. 56, 85-92. 2. Vallone, B., Nienhaus K., Matthes A., Brunori M., and Nienhaus G.U. (2004b) Proc. Natl. Acad. Sci. USA, 101,17351-17356. 3. Brunori M., Giuffrè A., Nienhaus K., Nienhaus G.U., Scandurra F.M., Vallone B. (2005) Proc. Natl Acad Sci U S A. 102,8483-8. 4. Anselmi M., Brunori M., Vallone B., Di Nola A. (2007) Biophys J. 93, 434-41. 5. Moschetti T., Mueller U., Schulze J., Brunori M., Vallone B. (2009) Biophys. J., 97, 1700-1708.
Appears in PhD:BIOFISICA

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