Figure 3. Residues in the NPxxY motif of D52N–UK432097 are neither in an entirely inactive or active-like conformation.

(a–d) Four conserved structural motifs (i.e. microswitches) labeled according to the amino acid types found in each motif. Within each panel, a superposition of A_2AAR–ZM241385 (yellow; PDB ID 3EML) with D52N–UK432097 (green) is on the left, and a superposition of A_2AAR–UK432097 (grey; PDB ID 3QAK) with D52N–UK432097 (green) is on the right. Amino acids comprising each structural motif are shown in stick representation and labeled by the Ballesteros-Weinstein nomenclature. Positions of the microswitches in the global structures are indicated by boxes in the middle superposition of all three structures. The location of residue D52N is indicated in the global view of the structure and labeled. Additionally, the binding sites of the orthosteric ligand (UK432097, cyan sticks), sodium (blue sphere), and G protein are shown in the center composite panel, where a surface representation of the mini Gα_s and its contacts with A_2AAR from the previously published A_2AAR–NECA–mini Gα_s complex structure (PDB ID 5G35) (Carpenter et al., 2016) are shown. See also Figure S2.