Structure and dynamics of Antarctic fish neuroglobin assessed by computer simulations

IGNACIO BORON, FLAVIO FORTI, ALEJANDRO D. NADRA Y DARIO ESTRIN

Congreso; XIV International Conference on Dioxygen Binding and Sensing Proteins; 2012

University of Parma

Neuroglobin (Ngb) is a new member of the globin family, evolutionarily conserved and predominantly expressed in nueronal tissue of vertebrates. Small ligands binds to the heme iron displacing distal histidine in the hexacoordinated ferrous state. Many species from the white-blooded icefish family channichthyids lack the genes encoding Hb and Mb while still produces the Ngb protein. This evidence suggests that the protein may have important implications in the physiology of these organisms but unfortunately physiological function of this protein is still unclear. We have previously described obtain the first theoretically derived structure of a colourless-blooded Antarctic icefish species Chaenocephalus aceratus, and a related red-blooded species (Dissostichus mawsoni) fish Ngb. Compared with mammalian Ngb, Antarctic fish proteins display some striking peculiarities in regions considered relevant for its function: (i) have extensions in the N and C termini that can interact with the EF loop (ii) CD region involved in heme coordination and in the ?His-gate?, are shorter by one residue. The shorter loop approaches two Cys allowing easy formation of the disulfide bridge. In this work, we explored Human Ngb and both Antarctic Ngbs huge inner cavity, connected to the solvent through the distal site and several other channels (Figure1). In particular, we focused in the the CO- and six-coordinated species, where alternative paths to the solvent present relatively low barriers. The comparison of structural and dynamic properties suggests that a multi-substrate reaction related function may be conserved along vertebrates and possibly improved in Antarctic fish Ngb.