Helokinestatin: A new bradykinin B2 receptor antagonist decapeptide from lizard venom

Because of significant differences in anatomy of the venom delivery system and distant phylogenetic relatedness, it had been long assumed that the venom systems of snakes and helodermatid lizards were independently evolved (1-3). However, both lineages were recently revealed to be members of a clade (Toxicofera) that also included several lineages of other lizards recently shown to be venomous (4, 5). In contrast to the hypothesis of independent origins, this new perspective revealed that lizard and snake venom systems are homologous but highly differentiated descendants of an early evolved venom system in squamates. The basal condition was incipient glands on both the mandibular and maxillary regions with snakes favoring the maxillary venom glands and secondarily losing the mandibular venom glands. However, the anguimorph lizards (anguids, helodermatids, and varanids) did the reverse, resulting in the modern condition seen today.The lizard venom delivery system is less sophisticated than the high pressure injection mechanism of the front fanged advanced snakes, and the vast majority of the species pose trivial direct medical risks to human (with the exception of helodermatids and large varanids such as Varanus komodoensis). However, the effects of envenomation from mediFrom the

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“…Bradykinin inhibition (22,24); bioactivity determined for new variants from anguid venoms in this study (Fig. 2D) …”

Section: Resultsmentioning

confidence: 82%

“…peptides (22,24). Helokinestatin peptides are thus a rare case of a single gene being mutated to additionally encode multiple products.…”

Section: Fig 1 Cladogram Of Evolutionary Relationships Of Representmentioning

confidence: 99%

Functional and Structural Diversification of the Anguimorpha Lizard Venom System

Fry

Winter

Norman

et al. 2010

Molecular & Cellular Proteomics

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“…"Exendin-2 long" is an intestinal vasoactive peptide that induces hypotension in prey mediated by the relaxation of the myocardium (Tsueshita et al, 2004) and "exendin-4", also hypotensive, mimetizes glucagon which led to the development of the antidiabetic Byetta ® , an insulin production stimulator (Furman, 2012). "Helokinestatin-1", derived from a decapeptide, antagonizes the bradykinin vasodilatation activity on B2 receptors of bradykinin (Kwok et al, 2008). Finally, "kallikrein-toxin", described at the cDNA level (Fry et al, 2010), is a kallikrein serine protease of unknown activity, with a sequence similar to gilatoxin (Utaisincharoen et al, 1993).…”

Section: Vip/glucagon-like Peptides and Heloderma Lizard Toxinsmentioning

confidence: 99%

Venomics of the Australian eastern brown snake ( Pseudonaja textilis ): Detection of new venom proteins and splicing variants

Viala

Hildebrand

Trusch

et al. 2015

Toxicon

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The eastern brown snake is the predominant cause of snakebites in mainland Australia. Its venom induces defibrination coagulopathy, renal failure and microangiopathic hemolytic anemia. Cardiovascular collapse has been described as an early cause of death in patients, but, so far, the mechanisms involved have not been fully identified. In the present work, we analysed the venome of Pseudonaja textilis by combining high throughput proteomics and transcriptomics, aiming to further characterize the components of this venom. The combination of these techniques in the analysis and identification of toxins, venom proteins and putative toxins allowed the sequence description and the identification of the following: prothrombinase coagulation factors, neurotoxic textilotoxin phospholipase A2 (PLA2) subunits and "acidic PLA2", three-finger toxins (3FTx) and the Kunitz-type protease inhibitor textilinin, venom metalloproteinase, C-type lectins, cysteine rich secretory proteins, calreticulin, dipeptidase 2, as well as evidences of Heloderma lizard peptides. Deep data-mining analysis revealed the secretion of a new transcript variant of venom coagulation factor 5a and the existence of a splicing variant of PLA2 modifying the UTR and signal peptide from a same mature protein. The transcriptome revealed the diversity of transcripts and mutations, and also indicates that splicing variants can be an important source of toxin variation.

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“…The pharmacological evaluations revealed that even acting in the same pathway, they can show distinct biological activities compared to BK, including potentiating its effects by inhibition of its degradation or by acting on receptors and/or molecules involved in the BK signaling pathway, including activating or blocking the BK receptors [10,35]. As such, the BRPs also include BPPs and the Bradykinin Inhibitor Peptides (BIPs) [13,29,32,36].…”

Section: Cdna Cloning Identification and Characterization Of Brpsmentioning

confidence: 99%

“…Helokinestatins are a family of proline-rich peptides (PRPs) found originally in the lizard venom (Heloderma suspectum) that display the function of inhibiting the BK actions on the vascular smooth muscle [35]. Synthetic replicates of all helokinestatins were found to antagonize the relaxation effect observed following BK application to a rat arterial smooth muscle preparation, and hence, represent a family of BRPs also known as BIPs [34].…”

Section: Bpps and Bipsmentioning

confidence: 99%

Venom Bradykinin-Related Peptides (BRPs) and Its Multiple Biological Roles

Lameu¹,

Neiva²,

Hayashi³

2013

An Integrated View of the Molecular Recognition and Toxinology - From Analytical Procedures to Biomedical Applications

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Helokinestatin: A new bradykinin B2 receptor antagonist decapeptide from lizard venom

Cited by 22 publications

References 23 publications

Functional and Structural Diversification of the Anguimorpha Lizard Venom System

Functional and Structural Diversification of the Anguimorpha Lizard Venom System

Venomics of the Australian eastern brown snake ( Pseudonaja textilis ): Detection of new venom proteins and splicing variants

Venom Bradykinin-Related Peptides (BRPs) and Its Multiple Biological Roles

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