Elapid Snake Venom Analyses Show the Specificity of the Peptide Composition at the Level of Genera Naja and Notechis

Abstract

Elapid snake venom is a highly valuable, but till now mainly unexplored, source of pharmacologically important peptides. We analyzed the peptide fractions with molecular masses up to 10 kDa of two elapid snake venoms—that of the African cobra, N. m. mossambica (genus Naja), and the Peninsula tiger snake, N. scutatus, from Kangaroo Island (genus Notechis). A combination of chromatographic methods was used to isolate the peptides, which were characterized by combining complimentary mass spectrometric techniques. Comparative analysis of the peptide compositions of two venoms showed specificity at the genus level. Three-finger (3-F) cytotoxins, bradykinin-potentiating peptides (BPPs) and a bradykinin inhibitor were isolated from the Naja venom. 3-F neurotoxins, Kunitz/basic pancreatic trypsin inhibitor (BPTI)-type inhibitors and a natriuretic peptide were identified in the N. venom. The inhibiting activity of the peptides was confirmed in vitro with a selected array of proteases. Cytotoxin 1 (P01467) from the Naja venom might be involved in the disturbance of cellular processes by inhibiting the cell 20S-proteasome. A high degree of similarity between BPPs from elapid and viperid snake venoms was observed, suggesting that these molecules play a key role in snake venoms and also indicating that these peptides were recruited into the snake venom prior to the evolutionary divergence of the snakes.

Revisiting Notechis scutatus venom: on shotgun proteomics and neutralization by the “bivalent” Sea Snake Antivenom

“…Of note, hemotoxic effects are rarely observed in envenomation by Asiatic elapids due to the absence of procoagulant and hemorrhagic enzymes in their venoms [27]. On the other hand, the identification of Kunitz-type serine protease inhibitors (~7%, KSPI) in this study is in agreement with previous findings of KSPI from transcription activity in the venom-gland [28] and protein isolation from the venom [29] of Australian tiger snake. The role of KSPI in N. scutatus envenomation is unclear but potentially related to the facilitation of presynaptic neurotoxicity through ion channel inhibition and chaperoning the neurotoxic PLA 2 s [30,31].…”

“…The occurrence of natriuretic peptide in this study (~2%) is also supported by the previous report on natriuretic peptide isolated from the venom [29]. This toxin may serve to induce hypotension, an effect that is probably important to aid in prey immobilization for the snake [29,32]. Other toxins detected at low abundance (b 2%) in this study were expressed proteins previously identified only at the level of transcription (L-amino acid oxidase, nerve growth factor, cysteine-rich secretory protein, vespryn), or have never been reported previously (acetylcholinesterase, 5′-nucleotidase, phospholipase B) for this species.…”

“…The role of KSPI in N. scutatus envenomation is unclear but potentially related to the facilitation of presynaptic neurotoxicity through ion channel inhibition and chaperoning the neurotoxic PLA 2 s [30,31]. The occurrence of natriuretic peptide in this study (~2%) is also supported by the previous report on natriuretic peptide isolated from the venom [29]. This toxin may serve to induce hypotension, an effect that is probably important to aid in prey immobilization for the snake [29,32].…”

Isolation and biochemical characterization of bradykinin-potentiating peptides from Bitis gabonica rhinoceros

“…After the discovery of these first BPPs, similar proline-rich peptides were isolated from different snake venoms [31–34] and even frogs skin secretion [35, 36]. …”

Proteomic analysis of the rare Uracoan rattlesnake Crotalus vegrandis venom: Evidence of a broad arsenal of toxins

“…Even with this accumulated history of success, new features are being discovered for BPPs in many different Viperidae venoms (e.g. Gomes et al, 2007;Rioli et al, 2008) and, even in Elapidae venom such as Naja mossambica (Munawar et al, 2014). Usually, BPP precursors are composed by BPPs, BIP and CNP, separated by propeptides that are cleaved into the active peptides.…”