PerspectiveBiochemistry

As Good as Chocolate

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Science  03 May 2013:
Vol. 340, Issue 6132, pp. 562-563
DOI: 10.1126/science.1238521

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Summary

No one could have imagined how important the 1948 discovery of the vasoconstrictor serotonin (5-hydroxytryptamine or 5-HT) would be to the field of human physiology (1). Elucidation of the 5-HT structure (2) and synthesis of the molecule with the expected biological activity (3) soon followed. This monoamine is a ligand for 15 receptors, and drugs that target 5-HT receptors are widely used to treat conditions including migraine headache, depression, anxiety, nausea, vomiting, and irritable bowel syndrome, reflecting the wide diversity of physiological and pathophysiological processes in which 5-HT is involved (4). On page 615 and 610 in this issue, Wacker et al. (5) and Wang et al. (6), respectively, report the crystal structure of human 5-HT2B bound to the antimigraine agent ergotamine and compare it with the 5-HT1B-ergotamine structure. Together with biochemical and computational data, these structures reveal molecular mechanisms responsible for divergent signaling patterns of ergotamine, serotonin, and the psychedelic drug lysergic acid diethylamide (LSD).