Sequence Variants of the Ligand-Binding Domain of the Glucocorticoid Receptor Gene and their Functional Consequences on the Three- Dimensional Protein Structure

Author(s): Istvan Liko, Peter Igaz, Attila Patocs, Szilvia Toth, Tamas Pazmany, Miklos Toth, Karoly Racz

Journal Name: Current Medicinal Chemistry

Volume 11 , Issue 24 , 2004

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Abstract:

In recent years several mutations and sequence polymorphisms of the glucocorticoid receptor gene have been described. The majority of mutations have been found in patients with a rare endocrinological abnormality, the glucocorticoid resistance syndrome. In addition, some sequence polymorphisms have been considered to contribute to various diseases, but unambiguous correlations have not been established yet. Here we present the results of an in silico study, which revealed previously undescribed sequence variants of the glucocorticoid receptor gene. Although the three-dimensional structure of the DNA-binding domain of the glucocorticoid receptor has been known for several years, the crystal structure of the ligand-binding domain of the receptor has been published only recently. Using a comparative protein modelling, we analysed the structural relevance of known mutations as well as novel sequence variants discovered by our in silico approach in the ligand-binding domain of the glucocorticoid receptor. We conclude that comparative protein modelling of these mutant receptor variants offers a useful means to predict the functional consequences of amino acid replacements and to correlate structural abnormalities with clinical findings.

Keywords: glucocorticoid receptor, mutations, ligand-binding domain, in silico

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Article Details

VOLUME: 11
ISSUE: 24
Year: 2004
Page: [3229 - 3237]
Pages: 9
DOI: 10.2174/0929867043363749
Price: $65

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