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The electron density of capsaicin is colored in red Residue important for capsaicin activation identified by mutagenesis and functional studies are colored in orange. (D) A zoom-in view of the capsaicin binding pocket.
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Lipid membrane boundaries are indicated by cyan disks. It is clear that capsaicin (electron density boxed by solid line) binds to the transmembrane domains.
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(C) High resolution structure of rat TRPV1 determined by cryo-EM (atomic model: 3J5R in PDB electron density map, 5777 in EMD). (B) Schematic diagram showing the topology of a TRPV1 subunit. The atoms forming hydrogen bonds with TRPV1 are highlighted in red. The vanillyl Head and hydrophobic Tail groups are shaded in orange and blue, respectively. Similar to other capsaicinoids, capsaicin contains a vanillyl group (which we refer to as the Head), an amide group (the Neck) and a fatty acid chain (the Tail) (Fig. Capsaicin was first isolated from paprika and cayenne in the late 19 th century (Thresh, 1876), with its chemical structure reported in 1923 (Nelson and Dawson, 1923). Among the capsaicinoids, capsaicin (( E)- N-8-methylnon-6-enamide) is the most abundant in quantity, though not much spicier than other capsaicinoids such as dihydrocapsaicin, homocapsaicin and homodihydrocapsaicin based on the Scoville scale (Scoville, 1912). Plants of the genus Capsicum, family Solanaceae such as chili peppers are the most common source of spiciness, as their fruits contain a group of pungent molecules named capsaicinoids. However, we humans are the only species that deliberately seeks spicy foods (Nilius and Appendino, 2013), while most animals are repelled by the irritating sensation. Many health benefits are believed to originate from chili pepper consumption (Szallasi and Blumberg, 1999). Indeed, spicy hot pot is a signature dish in southwest China and chili peppers are essential ingredients in Mexican cuisine. Many people over the world enjoy spiciness in foods.