IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
artículos
Título:
Molecular dynamics simulations of apocupredoxins: insights into the formation and stabilization of entatic copper sites
Autor/es:
ABRIATA LA; A. J. VILA; DAL PERARO M
Revista:
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY
Editorial:
SPRINGER
Referencias:
Lugar: Berlin; Año: 2014 vol. 132 p. 18 - 20
ISSN:
0949-8257
Resumen:
Cupredoxins perform copper-mediated long-range electron transfer (ET) in
biological systems. Their copper-binding sites have evolved to force
copper ions into ET-competent systems with decreased reorganization
energy, increased reduction potential, and a distinct electronic
structure compared with those of non-ET-competent copper complexes. The
entatic or rack-induced state hypothesis explains these special
properties in terms of the strain that the protein matrix exerts on the
metal ions. This idea is supported by X-ray structures of apocupredoxins
displaying "closed" arrangements of the copper ligands like those
observed in the holoproteins; however, it implies completely buried
copper-binding atoms, conflicting with the notion that they must be
exposed for copper loading. On the other hand, a recent work based on
NMR showed that the copper-binding regions of apocupredoxins are
flexible in solution. We have explored five cupredoxins in their
"closed" apo forms through molecular dynamics simulations. We observed
that prearranged ligand conformations are not stable as the X-ray data
suggest, although they do form part of the dynamic landscape of the
apoproteins. This translates into variable flexibility of the
copper-binding regions within a rigid fold, accompanied by fluctuations
of the hydrogen bonds around the copper ligands. Major conformations
with solvent-exposed copper-binding atoms could allow initial binding of
the copper ions. An eventual subsequent incursion to the closed state
would result in binding of the remaining ligands, trapping the closed
conformation thanks to the additional binding energy and the fastening
of noncovalent interactions that make up the rack.