A chemogenomic analysis of the transmembrane binding cavity of human G-protein-coupled receptors

作者：Surgand JS; Rodrigo J; Kellenberger E; Rognan D^*

来源：Proteins: Structure, Function, and Genetics , 2006, 62(2): 509-538.

DOI：10.1002/prot.20768

• amino acid sequences
• human G-protein-coupled receptors
• transmembrane domain
• bovine rhodopsin

The amino acid sequences of 369 human nonolfactory G-protein-coupled receptors (GPCRs) have been aligned at the seven transmembrane domain (TM) and used to extract the nature of 30 critical residues supposed-from the X-ray structure of bovine rhodopsin bound to retinal-to line the TM binding cavity of ground-state receptors. Interestingly, the clustering of human GPCRs from these 30 residues mirrors the recently described phylogenetic tree of full-sequence human GPCRs (Fredriksson et al., Mol Pharmacol 2003;63:12561272) with few exceptions. A TM cavity could be found for all investigated GPCRs with physicochemical properties matching that of their cognate ligands. The current approach allows a very fast comparison of most human GPCRs from the focused perspective of the predicted TM cavity and permits to easily detect key residues that drive ligand selectivity or promiscuity.

• 出版日期2006-2-1