INQUIMAE   12526
INSTITUTO DE QUIMICA, FISICA DE LOS MATERIALES, MEDIOAMBIENTE Y ENERGIA
Unidad Ejecutora - UE
artículos
Título:
Exploring the molecular basis of human manganese superoxide dismutase inactivation mediated by tyrosine 34 nitration
Autor/es:
MORENO DM, MARTI MA, DE BIASE PM, ESTRIN DA, DEMICHELIS V, RADI R, BOECHI L*
Revista:
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Editorial:
ELSEVIER SCIENCE INC
Referencias:
Año: 2011 vol. 507 p. 304 - 309
ISSN:
0003-9861
Resumen:
Manganese Superoxide Dismutase (MnSOD) is an essential
mitochondrial antioxidant enzyme that protects organisms against
oxidative damage, dismutating superoxide radical () into H2O2 and O2.
The active site of the protein presents a Mn ion in a distorted
trigonalbipyramidal environment, coordinated by H26, H74, H163, D159
and one −OH ion or H2O molecule. The catalytic cycle of the enzyme is a ping-pong mechanism involving Mn3+/Mn2+.
It is known that nitration of Y34 is responsible for enzyme
inactivation, and that this protein oxidative modification is found in
tissues undergoing inflammatory and degenerative processes. However, the
molecular basis about MnSOD tyrosine nitration affects the protein
catalytic function is mostly unknown.
In this work we
strongly suggest, using computer simulation tools, that Y34 nitration
affects protein function by restricting ligand access to the active
site. In particular, deprotonation of 3-nitrotyrosine increases
drastically the energetic barrier for ligand entry due to the absence of
the proton.
Our results for the WT and selected mutant
proteins confirm that the phenolic moiety of Y34 plays a key role in
assisting superoxide migration.