Molecular Dynamics Simulation of Antarctic Fish Neuroglobin

IGNACIO BORÓN, ALEJANDRO D. NADRA, LUCIANA CAPECE, MARCELO MARTÍ AND DARÍO ESTRIN

Salta

Congreso; Latin American Protein Society Meeting; 2010

Latin American Protein Society

Neuroglobin (Ngb) is a recently discovered globin that appeared 800 millon years ago. Mammalian Ngb exhibit a 20% sequence identity with Myoglobin but has 1/3 of its mutation rate. It is predominantly expressed in neuronal tissue and binds small gaseous ligands at the sixth coordination position of the heme iron.(1)? In the absence of an exogenous ligand, the distal histidine binds to the heme iron in the ferrous and ferric states. Recent studies revealed that the formation of an intramolecular disulfide bond in the CD region, increased O2 affinity by a factor of 10.(2) The white­blooded icefish family channichthyids do not express hemoglobin nor myoglobin while still produces the Ngb protein. In contrast to mammals, Ngb mutation rate, is very similar to Mb and, in addition to neuronal tissue, it is highly expressed in fish guts.(3) We have performed classical MD simulations in conjunction with advanced sampling techniques to obtain information about the key determinants for the penta to hexacoordination switch, the effect of disulfide bridge formation and the pattern of ligand migration. Here we present novel structures for the antarctic fish penta and hexa coordinated ferrous states. We have obtained a free energy profile for the 5c to 6c switch and evaluated the effect of a disulfide bridge in the CD region. Still in an early stage, the aims of this work is to evaluate the different activities suggested for this protein to finally find the (main) function (s) of Ngb in vivo.