BmK-YA, an enkephalin-like peptide in scorpion venom.
By screening extracts of venom from the Asian scorpion Buthus martensii Karsch (BmK) for their abilities to activate opioid receptors, we have identified BmK-YA, an amidated peptide containing an enkephalin-like sequence. BmK-YA is encoded by a precursor that displays a signal sequence and contains four copies of BmK-YA sequences and four of His(4)-BmK-YA, all flanked by single amino acid residues. BmK-YA and His(4)-BmK-YA are amidated and thus fulfill the characteristics expected of bioactive peptides. BmK-YA can activate mammalian opioid receptors with selectivity for the δ subtype while His(4)-BmK-YA is inactive at opioid receptors. The discovery of BmK-YA suggests that scorpion venom may represent a novel source of bioactive molecules targeting G protein-coupled receptors (GPCRs) and reveal additional insights on the evolution of the opioid precursors.
Department of Pharmacology, University of California Irvine, Irvine, California, United States of America.
Yan
Y
Zhang
Junyan
J
Xu
Zhiwei
Z
Wang
Xiuli
X
Zhang
Xinmiao
X
Liang
Olivier
O
Civelli
D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D060829:Arthropod Proteins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects; D003001:Cloning, Molecular; D004745:Enkephalins / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000819:agonists* / Q000378:metabolism; D012604:Scorpion Venoms / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D012605:Scorpions; D020539:Sequence Analysis, Protein
D000701:Analgesics, Opioid; D060829:Arthropod Proteins; D004745:Enkephalins; D011498:Protein Precursors; D011957:Receptors, Opioid; D012604:Scorpion Venoms