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Structural determinants of the alpha2 adrenoceptor subtype selectivity.

ABSTRACT: Alpha2-adrenergic receptor (?2-AR) subtypes, acting mainly on the central nervous and cardiovascular systems, represent important targets for drug design, confirmed by the high number of studies published so far. Presently, only a few ?2-AR subtype selective compounds are known. Using homology modeling and ligand docking, the present study analyzes the similarities and differences between binding sites, and between extracellular loops of the three subtypes of ?2-ARs. Several ?2-AR subtype selective ligands were docked into the active sites of the three ?2-AR subtypes, key interactions between ligands and receptors were mapped, and the predicted results were compared with the available experimental data. Binding site analysis reveals a strong identity between important amino acid residues in each receptor, the very few differences being the key toward modulating selectivity of ?2-AR ligands. The observed differences between binding site residues provide an excellent starting point for virtual screening of chemical databases, in order to identify potentially selective ligands for ?2-ARs.

SUBMITTER: Ostopovici-Halip L

PROVIDER: S-EPMC3307019 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Structural determinants of the alpha2 adrenoceptor subtype selectivity.

Ostopovici-Halip Liliana L Curpăn Ramona R Mracec Maria M Bologa Cristian G CG

Journal of molecular graphics & modelling 20110506 8

Alpha2-adrenergic receptor (α2-AR) subtypes, acting mainly on the central nervous and cardiovascular systems, represent important targets for drug design, confirmed by the high number of studies published so far. Presently, only a few α2-AR subtype selective compounds are known. Using homology modeling and ligand docking, the present study analyzes the similarities and differences between binding sites, and between extracellular loops of the three subtypes of α2-ARs. Several α2-AR subtype select ...[more]

PMID: 21602069

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Structural determinants of the alpha2 adrenoceptor subtype selectivity.

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Structural determinants of the alpha2 adrenoceptor subtype selectivity.

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