INQUIMAE   12526
INSTITUTO DE QUIMICA, FISICA DE LOS MATERIALES, MEDIOAMBIENTE Y ENERGIA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Exploring the molecular basis of heme hexacoordination by means of molecular dynamics simulations
Autor/es:
LUCIANA CAPECE; LEONARDO BOECHI; ALEJANDRO D. NADRA; AXEL BIDON-CHANAL; MARCELO A. MARTI; F. JAVIER LUQUE; DARÍO A. ESTRIN
Lugar:
Montevideo, Uruguay
Reunión:
Congreso; 6th International Conference of Biological Physics - 5th Southern Cone Biophysical Congress - 34th Annual meeting of the Argentinian Biophysical Society.; 2007
Resumen:
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Neuroglobin
(Ngb) and Cytoglobin (Cyb),
are two recently discovered human heme proteins. In contrast with
hemoglobin or myoglobin, their heme is hexacoordinated. The function
of these proteins is still unclear. Proposed functions for these
proteins include oxygen transport, reactive oxygen species
detoxification, hypoxia protection, and redox state sensing. For any
of the proposed functions, distal histidine dissociation from the
hemic iron is required. In addition, a disulfide bridge between two
cysteine residues is found in both proteins and might have an
important effect on the dissociation of the distal histidine.
With
the aim of understanding this hexa-penta coordination transition, we
have performed 50ns molecular dynamics simulations in explicit water
for ferrous Ngb in the hexacoordinated and pentacoordinated states.
We evaluated the effect of the redox state by means of performing
simulations of the protein with a disulfide bridge. We found that
protein oxidation promotes a decrease in the barrier for
pentacoordination and stabilizes the pentacoordinated species. The
key step to obtain the pentacoordinated protein appears to be a
distal histidine rotation which is concomitant with an upward
displacement of the E helix. In order to compare the results for Ngb
with another protein that displays an hexacoordinated heme, molecular
dynamics simulations of Cyb in the reduced and oxydized forms were
performed.