MD simulations of plant hemoglobins: the hexa- to penta-coordinate structural transition

Hemoglobins are ubiquitous proteins found in bacteria, plants, and animals with diverse functions other than the classical transport/storage of oxygen. Different functions are expected to correspond to substantially dif- ferent structures, such as the hexa- and penta-coordination of the iron atom. It is now widely believed that pentaco- ordinate hemoglobins evolved from the hexacoordinate ones, both in plants and in animals. Since plant hemoglo- bins evolved more recently than in animals, they represent a simpler and thus useful system to investigate protein sequence/structure features that specifically supported, guided by molecular evolution, the capacity for oxygen transport. In the present work, we selected a fully hexa- coordinate globin, AHb2 from Arabidopsis thaliana and the pentacoordinate oxygen-transporting LegHb from yellow lupin, that share a high degree of sequence identity. Our aim is to identify the structural determinants for oxygen transport by analyzing the structural/dynamical differences of a hexacoordinate and a pentacoordinate globin using all- atom molecular dynamics simulations. Using comparative MD simulations, we were able to go beyond the simple sequence alignment, pointing out important differences between these two hemoglobins especially at the level of the CD region, whose dynamics was found, in turn, to be strongly correlated with that of the distal region.