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

• Published in: Peptides (New York, N.Y. : 1980) Vol. 31; no. 8; pp. 1555 - 1561
• Main Authors: Zhang, Yao, Wang, Lei, Zhou, Mei, Zhou, Zhihao, Chen, Xiaole, Chen, Tianbao, Kwok, HangFai, Ivanyi, Craig, Shaw, Chris
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.08.2010; Elsevier
• Subjects: Amino Acid Sequence; Animals; Antagonist; Arteries; Arteries - drug effects; Attenuation; Base Sequence; Biological and medical sciences; Bradykinin; Bradykinin - antagonists & inhibitors; Bradykinin - pharmacology; Deletion; DNA, Complementary - chemistry; DNA, Complementary - genetics; Drug Discovery; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Lizard; Lizards - metabolism; Male; Mass spectrometry; Molecular cloning; Molecular Sequence Data; Molecular Weight; Muscle, Smooth, Vascular - drug effects; Muscles; Oligopeptides - chemistry; Oligopeptides - genetics; Oligopeptides - isolation & purification; Oligopeptides - pharmacology; Peptides; Precursors; Protein Isoforms - chemistry; Protein Isoforms - genetics; Protein Isoforms - isolation & purification; Protein Isoforms - pharmacology; Protein Precursors - chemistry; Protein Precursors - genetics; Protein Precursors - pharmacology; Rats; Rats, Wistar; Reproduction; Residues; Sequence Alignment; Sequence Analysis, DNA; Vasoconstriction - drug effects; Vasoconstrictor Agents - chemical synthesis; Vasoconstrictor Agents - chemistry; Vasoconstrictor Agents - isolation & purification; Vasoconstrictor Agents - pharmacology; Vasodilation - drug effects; Venom; Venoms - chemistry; Venoms - genetics; Venoms - isolation & purification; Venoms - pharmacology; Vertebrates: endocrinology; Antagonist; Molecular cloning; Mass spectrometry; Lizard; Venom; Bradykinin; Rat; Peptide hormone; Rodentia; Smooth muscle; Neuropeptide; Artery; Relaxation; Vertebrata; Mammalia; Blood vessel; Animal; Tail; Circulatory system
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2010.04.030

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.