Proteomic and Genomic Studies on Lizard Venoms in the Last Decade

Abstract

Abstract:Traditionally man has looked to nature to provide cures for diseases. This approach still exists today in the form of 'bio-prospecting' for therapeutically-active compounds in venoms. For example, the venoms of many reptiles offer a spectacular laboratory of bioactive molecules, including peptides and proteins. In the last 10-15 years, there have been a number of major proteomic and genomic research breakthroughs on lizard venoms. In this current review, the key findings from these proteomic and genomic studies will be critically discussed and suggestions will be offered for future focused investigations. It is our intention that this article will not only provide a comprehensive picture of the state of current knowledge of the components of lizard venoms, but also engender awareness in readers of the need to protect and conserve such uniquely precious natural resources for several reasons, including the potential benefit of humankind.

Article Commentary: Drug Discovery Benefits from Venomous Clues

“…In the recent review article by Kwok et al, 6 the concept of lizard (Lacerta) venoms as a potential source of biologically active therapeutic agents is critically surveyed. The review article discusses advances that have been made over the last several years in the development of minimally invasive procedures for harvesting lizard venoms.…”

“…The helodermatid lizards are considered one of the most important species of lizards that have attracted increasing attention because of the broad utility of their venoms for biomedical applications. 6 Kwok et al describe how the venoms collected from the helodermatid lizards have permitted discovery of novel bioactive agents such as the exendin peptide toxin (sold over the counter as Byetta TM ) for the treatment of diabetes. 6,11 Remarkably, Kwok et al discovered a novel bradykinin-receptor inhibitory peptide from the venom of helodermatid lizards which was named helokinestatin.…”

“…6 Kwok et al describe how the venoms collected from the helodermatid lizards have permitted discovery of novel bioactive agents such as the exendin peptide toxin (sold over the counter as Byetta TM ) for the treatment of diabetes. 6,11 Remarkably, Kwok et al discovered a novel bradykinin-receptor inhibitory peptide from the venom of helodermatid lizards which was named helokinestatin. 10 Clearly, this remains an evolving field of scientific and drug discovery where Kwok and others 10,12 have pioneered the way forward for novel drug discovery in lizard venoms.…”

The Dragon’s Paralysing Spell: Evidence of Sodium and Calcium Ion Channel Binding Neurotoxins in Helodermatid and Varanid Lizard Venoms

“…In addition to coagulotoxic, myotoxic and cytotoxic traits, Heloderma bites are often reported to cause pain, paresthesia, tachycardia and paralysis consistent with neurotoxic/cardiotoxic envenomation [ 23 , 25 , 26 ]. Previous research on Heloderma venom has revealed a myriad of protein families often recruited as neurotoxins [ 24 , 27 , 28 , 29 , 30 ]. However, few toxins have been isolated and characterized.…”

“…The toxins likely responsible for coagulotoxic activities in varanid lizards are kallikrein enzymes, which destructively cleave fibrinogen, and phospholipase A 2 (PLA 2 ), which block platelet aggregation, with both toxin types being homologous to Heloderma toxins with the same activity, reflective of their shared molecular evolutionary history and arising from the same venom glands [ 37 , 38 , 40 , 50 , 51 ]. However, many toxin families often recruited as neurotoxins in other organisms, such as AVIT, PLA 2 , cysteine rich secretory proteins (CRiSPs) and kunitz peptides, have been identified in the venom gland transcriptomes or venom proteomes of varanid and helodermatid lizards [ 15 , 24 , 27 , 28 , 29 , 30 , 37 , 40 ]. Indeed, the neurotoxic peptides in the AVIT and cholecystoxin classes were likely responsible for the strong contraction of rat smooth muscle after incubation with V. varius venom [ 37 , 38 ].…”