Hossein Batebi

Significance Recent structures of GPCRs in complex with G proteins provide important insights into G protein activation by family A and family B GPCRs; however, important questions remain. We don’t fully understand the mechanism of G protein coupling specificity or coupling promiscuity of some GPCRs. The β 2 AR preferentially couples to G s and less efficiently to G i , yet β 2 AR-G i coupling has been shown to play important roles in cardiac physiology. To better understand the structural basis for the preferential coupling of the β 2 AR to G s over G i , we used NMR spectroscopy and supporting MD simulations to study the conformational changes in the intracellular surface of the β 2 AR. These studies reveal a distinct difference in intracellular loop 2 interactions with G s and G i1 .

In this study, we have used density functional theory to identify a new mechanism for the formation of carboxylate compounds from heteroarenes, such as benzoxazole, in the presence of copper catalysts. This new mechanism involves the formation of a carbene intermediate that is indirectly stabilized by the electron-releasing copper. This intermediate carbene can isomerize to the experimentally observed resting state of the catalytic cycle, but it is the intermediate carbene itself that has the greater reactivity toward CO2 and that leads to the final carboxylate product via a lower-energy pathway. Our findings demonstrate the importance of considering metal-stabilized carbenes in such reactions. Our findings also suggest that this carbene intermediate can act as a nucleophile in other organometallic reactions.