@article{1fd5d4909d2d11debc73000ea68e967b,
title = "Ligand binding and micro-switches in 7TM receptor structures",
abstract = "The past couple of years have seen several novel X-ray structures of 7 transmembrane (7TM) receptors in complex with antagonists and even with a peptide fragment of a G protein. These structures demonstrate that the main ligand-binding pocket in 7TM receptors is like a funnel with a partial 'lid' in which extracellular loop 2b, in particular, functions as a gating element. Small-molecule antagonists and inverse agonists bind in very different modes: some very deeply and others more superficially, even reaching out above the transmembranes. Several highly conserved residues seem to function as micro-switches of which ArgIII:26 (Arg3.50) in its active conformation interacts directly with the G protein. These micro-switches together with a hydrogen-bond network between conserved polar residues and structural water molecules are proposed to constitute an extended allosteric interface between the domains (i.e. especially TM-VI), which performs the large, global toggle switch movements connecting ligand binding with intracellular signaling.",
author = "Rie Nygaard and Frimurer, {Thomas M} and Birgitte Holst and Rosenkilde, {Mette M} and Schwartz, {Thue W}",
note = "Keywords: Allosteric Regulation; Binding Sites; Drug Agonism; Drug Antagonism; Ligands; Models, Molecular; Molecular Conformation; Molecular Structure; Protein Interaction Domains and Motifs; Receptors, G-Protein-Coupled",
year = "2009",
doi = "10.1016/j.tips.2009.02.006",
language = "English",
volume = "30",
pages = "249--59",
journal = "TIPS - Trends in Pharmacological Sciences",
issn = "0165-6147",
publisher = "Elsevier Ltd. * Trends Journals",
number = "5",
}