title: Identification and functional analysis of a novel bradykinin inhibitory peptide in the venoms of New World Crotalinae pit vipers.
abstract: A novel undecapeptide has been isolated and structurally characterized from the venoms of three species of New World pit vipers from the subfamily, Crotalinae. These include the Mexican moccasin (Agkistrodon bilineatus), the prairie rattlesnake (Crotalus viridis viridis), and the South American bushmaster (Lachesis muta). The peptide was purified from all three venoms using a combination of gel permeation chromatography and reverse-phase HPLC. Automated Edman degradation sequencing and MALDI-TOF mass spectrometry established its peptide primary structure as: Thr-Pro-Pro-Ala-Gly-Pro-Asp-Val-Gly-Pro-Arg-OH, with a non-protonated molecular mass of 1063.18 Da. A synthetic replicate of the peptide was found to be an antagonist of bradykinin action at the rat vascular B2 receptor. This is the first bradykinin inhibitory peptide isolated from snake venom. Database searching revealed the peptide to be highly structurally related (10/11 residues) with a domain residing between the bradykinin-potentiating peptide and C-type natriuretic peptide domains of a recently cloned precursor from tropical rattlesnake (Crotalus durissus terrificus) venom gland. BIP thus represents a novel biological entity from snake venom.
authors.affiliation: School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, UK. rl.graham@ulster.ac.uk
authors.forename: Robert Leslie James
authors.initials: RL
authors.lastname: Graham
authors.forename: Ciaren
authors.initials: C
authors.lastname: Graham
authors.forename: Stephen
authors.initials: S
authors.lastname: McClean
authors.forename: Tianbao
authors.initials: T
authors.lastname: Chen
authors.forename: Martin
authors.initials: M
authors.lastname: O'Rourke
authors.forename: David
authors.initials: D
authors.lastname: Hirst
authors.forename: David
authors.initials: D
authors.lastname: Theakston
authors.forename: Chris
authors.initials: C
authors.lastname: Shaw
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001920:Bradykinin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003435:Crotalid Venoms / Q000737:chemistry*; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013623:Tail / Q000187:drug effects; D017819:Viperidae
chemical_list: D003435:Crotalid Venoms; D010455:Peptides; D001920:Bradykinin