INVESTIGADORES
ESTRIN Dario Ariel
artículos
Título:
The key role of water in the dioxygenase function of Escherichia coli flavohemoglobin
Autor/es:
D. FERREYRO; L. BOECHI; D.A. ESTRIN; M.A. MARTI
Revista:
JOURNAL OF INORGANIC BIOCHEMISTRY
Editorial:
ELSEVIER SCIENCE INC
Referencias:
Lugar: Amsterdam; Año: 2012 vol. 119 p. 75 - 84
ISSN:
0162-0134
Resumen:
Flavohemoglobins (FHbs) are members of the globin superfamily, widely distributed among prokaryotes and
eukaryotes that have been shown to carry out nitric oxide dioxygenase (NOD) activity. In prokaryotes, such
as Escherichia coli, NOD activity is a defence mechanism against the NO release by the macrophages of the
hosts' immune system during infection. Because of that, FHbs have been studied thoroughly and several
drugs have been developed in an effort to fight infectious processes. Nevertheless, the protein's structural
determinants involved in the NOD activity are still poorly understood. In this context, the aim of the present
work is to unravel the molecular basis of FHbs structural dynamics-to-function relationship using state of the
art computer simulation tools. In an effort to fulfill this goal, we studied three key processes that determine
NOD activity, namely i) ligand migration into the active site ii) stabilization of the coordinated oxygen and iii)
intra-protein electron transfer (ET). Our results allowed us to determine key factors related to all three
processes like the presence of a long hydrophobic tunnel for ligand migration, the presence of a water mediated
hydrogen bond to stabilize the coordinated oxygen and therefore achieve a high affinity, and the best
possible ET paths between the FAD and the heme, where water molecules play an important role. Taken
together the presented results close an important gap in our understanding of the wide and diverse globin
structural-functional relationships.