Structural and functional studies of the human selenium binding protein-1 and its involvement in hepatocellular carcinoma.
Biochim Biophys Acta
; 1814(4): 513-22, 2011 Apr.
Article
em En
| MEDLINE
| ID: mdl-21338716
ABSTRACT
The reduced expression of human selenium binding protein-1 (SELENBP1) has been reported for some human cancers. In this work we have estimated a reduced SELENBP1 expression by immunohistochemistry for the first time also in liver tissues of patients with hepatocarcinoma (HCC). Since the structure-function relationships of SELENBP1 are unknown, we have performed computational and experimental studies to have insight on the structural features of this protein focusing our attention on the properties of cysteines to assess their ability to interact with selenium. We have performed CD studies on the purified protein, modeled its three-dimensional structure, studied the energetic stability of the protein by molecular dynamics simulations, and titrated the cysteines by DTNB (5,5'-dithiobis (2-nitrobenzoic acid). The secondary structure content evaluated by CD has been found similar to that of 3D model. Our studies demonstrate that (i) SELENBP1 is an alpha-beta protein with some loop regions characterized by the presence of intrinsically unordered segments, (ii) only one cysteine (Cys57) is enough exposed to solvent, located on a loop and surrounded by charged and hydrophobic residues, and can be the cysteine able to bind the selenium. Furthermore, during the molecular dynamics simulation at neutral pH the loop containing Cys57 opens and exposes this residue to solvent, confirming that it is the best candidate to bind the selenium. Experimentally we found that only one cysteine is titratable by DTNB. This supports the hypothesis that Cys57 is a residue functionally important and this may open new pharmacological perspectives.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma Hepatocelular
/
Proteínas de Ligação a Selênio
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Neoplasias Hepáticas
Limite:
Aged
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Itália