Can the Partial Peptide SIVSF of the β-Adrenergic Receptor Recognize Chirality of the Epinephrine Neurotransmitter?

Chirality plays an essential role in biological molecular recognition, such as neurotransmission. Here, we applied electrospray-cold ion trap spectroscopy to complexes of a partial binding motif SIVSF of a β-adrenergic receptor pocket with L- and D-epinephrine AdH. The ultraviolet spectrum of the SIVSF-AdH complex changed drastically when L-AdH was replaced by its enantiomer. The isomer-selected infrared spectra revealed that D-AdH was bound to SIVSF by its protonated amino-group or a single catechol OH and induced nonhelical secondary structures of SIVSF. This is in sharp contrast to the helical SIVSF complex with L-AdH, which is close to the natural binding structure with two catechol OHs binding in the receptor. This shows that a short pentapeptide SIVSF can distinguish the chirality of the ligand AdH as well as the receptor. This stereoselectivity is suggested to arise from an additional interaction involving the hydroxyl group on the chiral carbon.