Figure 5.

Origin of the functional effect of mGlu₂ PAMs and mGlu₂ NAMs. A combined experimental and computational study by Perez-Benito et al. [82] showed that PAMs and NAMs bind above the transmission switch but transmit a different conformational effect. Based on the modelling, amino acids in the transmission switch were proposed for experimental mutagenesis that confirmed their importance for receptor activation. Thus, validating a hypothesis of local allosteric modulator induced conformational changes that promote or block movements of amino acids responsible for functional activity, overall confirming the 7TM analogy with class A GPCRs.