title: Molecular characterisation of endogenous snake venom metalloproteinase inhibitors.
abstract: Viper venoms contain one of the most potent mixtures of proteases in natural existence and yet the venom gland and proteins in this mixture are refractory to degradation. Here we demonstrate that the sub-10-kDa components of venom from two African viper species (Echis ocellatus and Cerastes cerastes cerastes) are predominantly composed of the tri-peptide pyroglutamate-lysine-tryptophan (pEKW). This tripeptide is encoded by tandemly repeating elements and, in E. ocellatus, on the same transcript as a novel, and highly unusual, poly-histidine-poly-glycine peptide (pHpG) also detected in E. ocellatus venom. The pEKW and pHpG peptides inhibit the proteolytic activity of the haemorrhagic snake venom metalloproteinase (SVMP), EoVMP-2, and the haemorrhagic activity of E. ocellatus venom. These results demonstrate that these vipers express abundant transcripts encoding tandemly repeated protease inhibitor cassettes and accumulate significant quantities of peptide inhibitors in venoms to provide a basis for attenuating the proteolytic activity of SVMPs.
authors.affiliation: Alistair Reid Venom Research Unit, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Wagstaff
authors.forename: Philippe
authors.initials: P
authors.lastname: Favreau
authors.forename: Olivier
authors.initials: O
authors.lastname: Cheneval
authors.forename: Gavin D
authors.initials: GD
authors.lastname: Laing
authors.forename: Mark C
authors.initials: MC
authors.lastname: Wilkinson
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Miller
authors.forename: Reto
authors.initials: R
authors.lastname: Stöcklin
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrison
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D045726:Metalloproteases / Q000037:antagonists & inhibitors*; D008969:Molecular Sequence Data; D014757:Viper Venoms / Q000737:chemistry* / Q000235:genetics*
chemical_list: D014757:Viper Venoms; D045726:Metalloproteases