Trends in pharmacological science, Volume 36, Issue 1, p22–31, January 2015

Abstract

Generic residue numbers facilitate comparisons of, for example, mutational effects, ligand interactions, and structural motifs. The numbering scheme by Ballesteros and Weinstein for residues within the class A GPCRs (G protein-coupled receptors) has more than 1100 citations, and the recent crystal structures for classes B, C, and F now call for a community consensus in residue number- ing within and across these classes. Furthermore, the structural era has uncovered helix bulges and constric- tions that offset the generic residue numbers. The use of generic residue numbers depends on convenient access by pharmacologists, chemists, and structural biologists. We review the generic residue numbering schemes for each GPCR class, as well as a complementary structure- based scheme, and provide illustrative examples and GPCR database (GPCRDB) web tools to number any receptor sequence or structure.

Alignment of the class-specific generic residue numbers based on structural alignment of crystal structures of representative receptors from class A (bovine rhodopsin, bRho), B (glucagon receptor), C (metabotropic glutamate receptor 1, mGlu1), and F (Smoothene, SMO). Class-specific reference residue positions (X.50) for each of the seven TM helices are given in bold font.

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