Non-enzymatic proteins from snake venoms: A gold mine of pharmacological tools and drug leads

McCleary, Ryan J.R.; Kini, R. Manjunatha

doi:10.1016/j.toxicon.2012.09.008

Cited by 128 publications

(68 citation statements)

References 150 publications

(151 reference statements)

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“…Briefly, the standard Q-Exactive quadrupole rf drive was modified in order to decrease the resonant rf frequency to 284 kHz and enable higher m/z selection up to m/z 20,000, as described previously (23). Scans were collected manually using 15,000 resolving power at m/z 200 for MS 1 spectra and 120,000 resolving power for MS 2 and pseudo-MS 3 spectra as described previously (23). Average masses and charge states for spectra without isotopic resolution were calculated by optimizing the standard deviation of the most intense peaks using the web tool ESIprot Online (41).…”

Section: Methodsmentioning

confidence: 99%

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Mapping Proteoforms and Protein Complexes From King Cobra Venom Using Both Denaturing and Native Top-down Proteomics

Melani¹,

Skinner

Fornelli

et al. 2016

Molecular & Cellular Proteomics

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Characterizing whole proteins by top-down proteomics avoids a step of inference encountered in the dominant bottom-up methodology when peptides are assembled computationally into proteins for identification. The direct interrogation of whole proteins and protein complexes from the venom of Ophiophagus hannah (king cobra) provides a sharply clarified view of toxin sequence variation, transit peptide cleavage sites and post-translational modifications (PTMs) likely critical for venom lethality. A tube-gel format for electrophoresis (called GELFrEE) and solution isoelectric focusing were used for protein fractionation prior to LC-MS/MS analysis resulting in 131 protein identifications (18 more than bottom-up) and a total of 184 proteoforms characterized from 14 protein toxin families. Operating both GELFrEE and mass spectrometry to preserve non-covalent interactions generated detailed information about two of the largest venom glycoprotein complexes: the homodimeric L-amino acid oxidase (ϳ130 kDa) and the multichain toxin cobra venom factor (ϳ147 kDa). The L-amino acid oxidase complex exhibited two clusters of multiproteoform complexes corresponding to the presence of 5 or 6 N-glycans moieties, each consistent with a distribution of N-acetyl hexosamines. Employing top-down proteomics in both native and denaturing modes provides unprecedented characterization of venom proteoforms and their complexes. A precise molecular inventory of venom proteins will propel the study of snake toxin variation and the targeted development of new antivenoms or other biotherapeutics. Molecular &

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Section: Methodsmentioning

confidence: 99%

“…The toxic secretions of venomous animals have long been a source of biologically active molecules, yet remain a promising source of new drugs (1,2). Snake venoms in particular are widely studied and contain a mixture of small molecules, peptides, proteins, and protein complexes which are used to incapacitate prey and to defend against predators (3)(4)(5).…”

mentioning

confidence: 99%

Mapping Proteoforms and Protein Complexes From King Cobra Venom Using Both Denaturing and Native Top-down Proteomics

Melani¹,

Skinner

Fornelli

et al. 2016

Molecular & Cellular Proteomics

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“…The first mechanism involved is the presence of proteases as kallikreins in the venom which act on plasma kininogen obtaining bradykinin, a potent vasodilator. The second mechanism is that those venoms contain peptides (angiotensin-converting enzyme inhibitors (ACEi)) of low molecular weight, which additionally induce bradykinin potentiation (BPPs) by inhibiting its degradation (Ferreira 1965;Soares et al 2005;McCleary and Kini 2013). The third mechanism is the presence of natriuretic peptides in the venom, natural inducers of diuresis and vascular relaxation (Soares et al 2005).…”

Section: Hypotensionmentioning

confidence: 99%

Snakebites in Colombia

Otero-Patiño

2014

Toxinology

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Nearly 4,000 snakebites are annually reported in Colombia -90-95 % are inflicted by pit vipers from Bothrops, Porthidium, Bothriechis, Bothriopsis, and Bothrocophias genera, specially by B. asper (50-80 %); 2 % by the bushmaster Lachesis spp.; 1 % by the rattle snake Crotalus durissus cumanensis; 1 % by coral snakes (Micrurus spp.); and the remaining 1-5 % by snakes of aglyphous and opisthoglyphous dentition, mainly from Colubridae family. The Colombian fatality rate of snakebite envenoming is 1-3 %, the highest percentage in the Orinochian and Amazonian regions, whereas 6 % of patients suffer some type of sequelae, mainly as a result of dermonecrosis and myonecrosis. B. asper is responsible for 60-90 % of deaths secondary to snakebites. In this chapter, the clinical and epidemiological aspects of bothropic, lachesic, crotalic, and elapidic envenomations are described, with specific features for the country, as well as the actual knowledge of venom composition and actions.

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“…Of particular note, the biodiversity of oceanic islands is often underestimated [9]. In addition to the ecological impact of a decrease in snake species richness, these extinctions have economic consequences: venoms have applications in many fields including medicine, pharmacology and immunology [10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Vintage venoms: Proteomic and pharmacological stability of snake venoms stored for up to eight decades

Jesupret

Baumann

Jackson

et al. 2014

Journal of Proteomics

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For over a century, venom samples from wild snakes have been collected and stored around the world. However, the quality of storage conditions for "vintage" venoms has rarely been assessed. The goal of this study was to determine whether such historical venom samples are still biochemically and pharmacologically viable for research purposes, or if new sample efforts are needed. In total, 52 samples spanning 5 genera and 13 species with regional variants of some species (e.g., 14 different populations of Notechis scutatus) were analysed by a combined proteomic and pharmacological approach to determine protein structural stability and bioactivity. When venoms were not exposed to air during storage, the proteomic results were virtually indistinguishable from that of fresh venom and bioactivity was equivalent or only slightly reduced. By contrast, a sample of Acanthophis antarcticus venom that was exposed to air (due to a loss of integrity of the rubber stopper) suffered significant degradation as evidenced by the proteomics profile. Interestingly, the Keywords:Mass spectrometry Toxinology Stability studies These results demonstrate that with proper storage techniques, venom samples can retain structural and pharmacological stability. This article is part of a Special Issue entitled:Proteomics of non-model organisms. Biological significance• These results show that with proper storage venoms are useful for decades.• These results have direct implications for the use of rare venoms.

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Non-enzymatic proteins from snake venoms: A gold mine of pharmacological tools and drug leads

Cited by 128 publications

References 150 publications

Mapping Proteoforms and Protein Complexes From King Cobra Venom Using Both Denaturing and Native Top-down Proteomics

Mapping Proteoforms and Protein Complexes From King Cobra Venom Using Both Denaturing and Native Top-down Proteomics

Snakebites in Colombia

Vintage venoms: Proteomic and pharmacological stability of snake venoms stored for up to eight decades

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