TABLE 2

Description of binding residues for THIQ and antagonists of the study

Residues of MC4R located at 4.5 or 4.0 Å from PCs docked in the models of MC4R receptor in the inactive conformation. Residues that are important for THIQ binding (Protein Data Bank code 2IQU) are in bold. Residues presented in Supplemental Fig. 2 are underlined.

PCTHIQMTHPaMTHPbPPPoneMCPIDCPMPNBP
Radius, Å4.5/4.04.5/4.04.5/4.04.5/4.04.5/4.04.5/4.04.5/4.0
NT
    Leu44+/++/+−/−+/++/+−/−+/+
TM2
    Glu100+/++/+−/−+/++/++/−+/+
    Val103+/−+/+−/−+/−+/+−/−+/+
    Ile104−/−+/+−/−+/++/+−/−+/+
TM3
    Asp122+/++/+−/−−/−−/−+/++/+
    Asp126+/++/++/++/++/++/++/+
    Ile129+/++/++/−+/++/++/++/+
    Cys130+/+−/−+/++/−+/++/−+/+
    Leu133+/−−/−+/++/−+/++/++/−
TM4
    Phe184+/+−/−+/−+/−−/−+/++/−
    Ile185−/−−/−+/++/−−/−+/++/−
EXL2
    Ser190−/−−/−−/−−/−−/−+/+−/−
    Ser191−/−−/−−/−−/−−/−+/−−/−
    Ala192+/+−/−−/−+/+−/−+/−+/+
    Val193+/+−/−−/−−/−−/−−/−+/−
TM5
    Cys196+/+−/−−/−−/−−/−−/−+/+
    Cys200+/+−/−+/++/++/++/++/+
TM6
    Phe261+/+−/−+/−+/++/++/++/+
    Phe262−/−−/−+/−−/−+/++/−−/−
    Leu265+/+−/−+/++/++/++/−+/+
    His264+/+−/−−/−−/−−/−−/−−/−
    Tyr268+/+−/−−/−−/−−/−−/−−/−
TM7
    Asn285+/++/+−/−+/−+/+−/−+/−
    Leu288+/++/+−/−+/++/++/−+/+
    Phe284+/+−/−−/−−/−−/−−/−−/−
    Met292+/−−/−−/−−/−−/−−/−−/−
  • NT, N terminus; MTHPa, binds between TM2, TM3, and TM7; MTHPb, binds between TM3 and TM6.