Snake Venom Phospholipase A2: Evolution and Diversity

Wong

et al. 2019

Toxins

The protein abundances of phospholipases A2 in cobra venom proteomes appear to vary among cobra species. To determine the unique distribution of snake venom phospholipases A2 (svPLA2) in the cobras, the svPLA2 activities for 15 cobra species were examined with an acidimetric and a colorimetric assay, using egg yolk suspension and 4-nitro-3-octanoyloxy benzoic acid (NOBA) as the substrate. The colorimetric assay showed significant correlation between svPLA2 enzymatic activities with the svPLA2 protein abundances in venoms. High svPLA2 activities were observed in the venoms of Asiatic spitting cobras (Naja sputatrix, Naja sumatrana) and moderate activities in Asiatic non-spitters (Naja naja, Naja atra, Naja kaouthia), African spitters (subgenus Afronaja), and forest cobra (subgenus Boulengerina). African non-spitting cobras of subgenus Uraeus (Naja haje, Naja annulifera, Naja nivea, Naja senegalensis) showed exceptionally low svPLA2 enzymatic activities. The negligible PLA2 activity in Uraeus cobra venoms implies that PLA2 may not be ubiquitous in all snake venoms. The svPLA2 in cobra envenoming varies depending on the cobra species. This may potentially influence the efficacy of cobra antivenom in specific use for venom neutralization.

Section: Introductionmentioning

confidence: 99%

Distinctive Distribution of Secretory Phospholipases A2 in the Venoms of Afro-Asian Cobras (Subgenus: Naja, Afronaja, Boulengerina and Uraeus)

Wong

et al. 2019

Toxins

“…PLA 2 s are found in the venoms of vipers, elapids, and certain rear-fanged species [ 57–60 ] and exert a wide variety of cytotoxic, myotoxic, cardiotoxic, and neurotoxic effects [ 57 , 58 , 60 ]. Of particular interest is a catalytically inactive, myotoxic category of PLA 2 s stemming from a single substitution of a highly conserved amino acid residue (Asp49 to Lys49/Asn49) [ 57 ].…”

Section: Current Status Of Snake Venom Researchmentioning

confidence: 99%

“…Both non-catalytic and enzymatic PLA 2 s are able to form heterodimeric complexes with other PLA 2 s or other toxins in certain venoms, whereby their toxicity is greatly potentiated [ 58 ]. Most snake genomes contain multiple PLA 2 genes, which likely originated from repeated gene duplication events [ 60 , 61 ]. These paralogs have diverse pharmacological activities, which were likely acquired through neofunctionalization (i.e., recruitment of a paralog to the venom gland following gene duplication and its subsequent evolution into a toxin-coding gene) [ 62 , 63 ].…”

Section: Current Status Of Snake Venom Researchmentioning

confidence: 99%

The rise of genomics in snake venom research: recent advances and future perspectives

et al. 2022

Snake venoms represent a danger to human health, but also a gold mine of bioactive proteins that can be harnessed for drug discovery purposes. The evolution of snakes and their venom has been studied for decades, particularly via traditional morphological and basic genetic methods alongside venom proteomics. However, while the field of genomics has matured rapidly over the past 2 decades, owing to the development of next-generation sequencing technologies, snake genomics remains in its infancy. Here, we provide an overview of the state of the art in snake genomics and discuss its potential implications for studying venom evolution and toxinology. On the basis of current knowledge, gene duplication and positive selection are key mechanisms in the neofunctionalization of snake venom proteins. This makes snake venoms important evolutionary drivers that explain the remarkable venom diversification and adaptive variation observed in these reptiles. Gene duplication and neofunctionalization have also generated a large number of repeat sequences in snake genomes that pose a significant challenge to DNA sequencing, resulting in the need for substantial computational resources and longer sequencing read length for high-quality genome assembly. Fortunately, owing to constantly improving sequencing technologies and computational tools, we are now able to explore the molecular mechanisms of snake venom evolution in unprecedented detail. Such novel insights have the potential to affect the design and development of antivenoms and possibly other drugs, as well as provide new fundamental knowledge on snake biology and evolution.

“…Synergistic action of kallikrein-like SVSPs and BPP has been suggested as they increase BK concentration through different pathways [56,97]. BPPs, NPs and SVSPs are characteristic for neurotoxic Viperidae venoms indicating possible coevolution of hypotensive and paralyzing snake venom strategies [98].…”

Section: Snake Venom Components With Hypotensive Effectsmentioning

confidence: 99%

Hypotensive Snake Venom Components—A Mini-Review

et al. 2019

Hypertension is considered a major public health issue due to its high prevalence and subsequent risk of cardiovascular and kidney diseases. Thus, the search for new antihypertensive compounds remains of great interest. Snake venoms provide an abundant source of lead molecules that affect the cardiovascular system, which makes them prominent from a pharmaceutical perspective. Such snake venom components include bradykinin potentiating peptides (proline-rich oligopeptides), natriuretic peptides, phospholipases A2, serine-proteases and vascular endothelial growth factors. Some heparin binding hypotensive factors, three-finger toxins and 5′ nucleotidases can also exert blood pressure lowering activity. Great advances have been made during the last decade regarding the understanding of the mechanism of action of these hypotensive proteins. Bradykinin potentiating peptides exert their action primarily by inhibiting the angiotensin-converting enzyme and increasing the effect of endogenous bradykinin. Snake venom phospholipases A2 are capable of reducing blood pressure through the production of arachidonic acid, a precursor of cyclooxygenase metabolites (prostaglandins or prostacyclin). Other snake venom proteins mimic the effects of endogenous kallikrein, natriuretic peptides or vascular endothelial growth factors. The aim of this work was to review the current state of knowledge regarding snake venom components with potential antihypertensive activity and their mechanisms of action.