Three-dimensional models of alpha(2A)-adrenergic receptor complexes provide a structural explanation for ligand binding

Tiina Salminen, M Varis, T Nyrönen, M Pihlavisto, AM Hoffren, T Lönnberg, A Marjamäki, H Frang, JM Savola, M Scheinin, Mark S Johnson

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

36 Citeringar (Scopus)


We have compared bacteriorhodopsin-based (alpha(2A)-AR(BR)) and rhodopsin-based (alpha(2A)-AR(R)) models of the human alpha(2A)-adrenengic receptor (alpha(2A)-AR) using both docking simulations and experimental receptor alkylation studies with chloroethylclonidine and a-aminoethyl methanethiosulfonate hydrobromide. The results indicate that the alpha(2A)-AR(R) model provides a better explanation for ligand binding than does our alpha(2A)-AR(BR) model. Thus, we have made an extensive analysis of ligand binding to alpha(2A)-AR(R) and engineered mutant receptors using clonidine, para-aminoclonidine, oxymetazoline, 5-bromo-N-(4, 5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK14,304), and norepinephrine as ligands, The representative docked ligand conformation was chosen using extensive docking simulations coupled with the identification of favorable interaction sites for chemical groups in the receptor, These ligand-protein complex studies provide a rational explanation at the atomic level for the experimentally observed binding affinities of each of these ligands to the alpha(2A)-adrenergic receptor.
Sidor (från-till)23405–23413
Antal sidor9
TidskriftJournal of Biological Chemistry
StatusPublicerad - 1999
MoE-publikationstypA1 Tidskriftsartikel-refererad

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