The second extracellular loop of alpha2A-adrenoceptors contributes to the binding of yohimbine analogues.

ABSTRACT:

Background and purpose

Rodent alpha(2A)-adrenoceptors bind the classical alpha(2)-antagonists yohimbine and rauwolscine with lower affinity than the human alpha(2A)-adrenoceptor. A serine-cysteine difference in the fifth transmembrane helix (TM; position 5.43) partially explains this, but all determinants of the interspecies binding selectivity are not known. Molecular models of alpha(2A)-adrenoceptors suggest that the second extracellular loop (XL2) folds above the binding cavity and may participate in antagonist binding.

Experimental approach

Amino acids facing the binding cavity were identified using molecular models: side chains of residues 5.43 in TM5 and xl2.49 and xl2.51 in XL2 differ between the mouse and human receptors. Reciprocal mutations were made in mouse and h

SUBMITTER: Laurila JM 

PROVIDER: S-EPMC2189838 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature