Table 1 Alignment of hydrophobic pocket residues for select GPCRs.

The amino acid position in extracellular loop 2 (EL2) is delineated using the nomenclature developed by de Graaf et al. (76). Yellow indicates nonpolar amino acids with an aliphatic group (Ala, Val, Ile, Leu, Met, and Gly); light green indicates hydrophobic amino acids with an aromatic ring (Phe and Tyr); dark green indicates Trp; purple indicates polar amino acids with an uncharged side chain (Ser, Thr, Asn, and Gln); light gray indicates Pro; red indicates negatively charged amino acids (Glu and Asp); and blue indicates positively charged amino acids (Arg, His, and Lys).

GPCRECL2-TM5 sequence*
45.525.355.365.375.385.395.40
D1RSerSerArgThrTyrAlaIle
D2RIleAsnProAlaPheValVal
D3RIleAsnProAspPheValIle
D4RLeuAspArgAspTyrValVal
D5RSerAsnArgThrTyrAlaIle
5-HT1ARIleAspHisGlyTyrThrIle
5-HT1BRValHisIleLysTyrThrVal
5-HT2ARLeuAspAspAsnPheValLeu
5-HT2BRLeuPheGlyAspPheMetLeu
5-HT2CRLeuAspProAsnPheValLeu
α1AIleGluProGlyTyrValLeu
α1BValGluProPheTyrAlaLeu
α1DIleGluAlaGlyTyrAlaVal
α2AIleGlnLysTrpTyrValIle
α2BLeuGluAlaTrpTyrIleLeu
α2CLeuGluThrTrpTyrIleLeu
β1RPheGlnArgAlaTyrAlaIle
β2RPheGlnGlnAlaTyrAlaIle
β3RPheGlnMetProTyrValLeu
V2RAlaArgArgThrTyrValThr

*Amino acid positions in transmembrane (TM) regions are delineated using the Ballesteros and Weinstein nomenclature (29).