The structure of helokinestatin-5 and its biosynthetic precursor from Gila monster (Heloderma suspectum) venom: evidence for helokinestatin antagonism of bradykinin-induced relaxation of rat tail artery smooth muscle.
Here we report the primary structure of a novel peptide, named helokinestatin-5 (VPPPLQMPLIPR), from the venom of the Gila monster (Heloderma suspectum). Helokinestatin-5 differs in structure from helokinestatin-3 by deletion of a single prolyl residue in the N-terminally located polyproline region. Two different biosynthetic precursors were consistently cloned from a venom-derived cDNA library. The first encoded helokinestatins 1-4 and a single copy of C-type natriuretic peptide, as previously described, whereas the second was virtually identical, lacking only a single prolyl codon as found in the mature attenuated helokinestatin-5 peptide. Helokinestatins 1-3 and 5 were synthesized by solid-phase fmoc chemistry and each synthetic replicate was found to antagonize the relaxation effect induced by bradykinin on rat tail artery smooth muscle. Helokinestatins thus represent a novel family of vasoactive peptides from the venom of helodermatid lizards.
Zhang
Yao
Y
Molecular Therapeutics Research, School of Pharmacy, Queen's University, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
Wang
Lei
L
Zhou
Mei
M
Zhou
Zhihao
Z
Chen
Xiaole
X
Chen
Tianbao
T
Kwok
HangFai
H
Ivanyi
Craig
C
Shaw
Chris
C
D000595:Amino Acid Sequence; D000818:Animals; D001158:Arteries / Q000187:drug effects; D001483:Base Sequence; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D055808:Drug Discovery; D066298:In Vitro Techniques; D008116:Lizards / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology; D011498:Protein Precursors / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014688:Venoms / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology
D018076:DNA, Complementary; D009842:Oligopeptides; D020033:Protein Isoforms; D011498:Protein Precursors; D014662:Vasoconstrictor Agents; D014688:Venoms; C527846:helokinestatin; D001920:Bradykinin