Potassium channel blockers from the venom of the Brazilian scorpion Tityus serrulatus ( )

Martin‐Eauclaire, Marie‐France; Pimenta, Adriano M.C.; Bougis, Pierre E.; Lima, Maria-Elena De

doi:10.1016/j.toxicon.2016.06.016

Cited by 16 publications

(6 citation statements)

References 68 publications

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“…In the venom of C. edwardsii, two more fragments (CedP1a and CedP2a) were detected, matching peptides affecting potassium channels, and were described as potent inhibitors of voltage-gated potassium channels [ 40 , 41 ]. Although there is no previous report of the peptide or protein content of these two Buthidae scorpions from Colombia ( T. asthenes and C. edwardsii ), venom characterization of other Buthidae indicates that neurotoxins are the major content of these venoms, just as seen in our results [ 42 - 44 ]. We found four more fragments (TaP1a, TaP1b, TaP14a and CedP4a) from T. asthenes and C. edwardsii that are similar to antimicrobial peptides (AMP), active against Gram-negative and Gram-positive bacteria and fungi [ 13 ].…”

Section: Discussionsupporting

confidence: 59%

MS/MS analysis of four scorpion venoms from Colombia: a descriptive approach

Estrada-Gómez

Muñoz

Saldarriaga‐Córdoba

et al. 2021

J. Venom. Anim. Toxins incl. Trop. Dis

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Background: Scorpions are widely known for the neurotoxic effects of their venoms, which contain peptides affecting ionic channels. Although Colombia is recognized for its scorpion diversity, only a few studies are available describing the venom content. Methods: In this descriptive study, we analyzed the MS/MS sequence, electrophoretic and chromatographic profile linked to a bioinformatics analysis of the scorpions Chactas reticulatus (Chactidae), Opisthacanthus elatus (Hormuridae), Centruroides edwardsii (Buthidae) and Tityus asthenes (Buthidae) from Colombia. Results: Each scorpion showed a specific electrophoretic and chromatographic profile. The electrophoretic profiles indicate the presence of high molecular mass compounds in all venoms, with a predominance of low molecular mass compounds in the Buthidae species. Chromatographic profiles showed a similar pattern as the electrophoretic profiles. From the MS/MS analysis of the chromatographic collected fractions, we obtained internal peptide sequences corresponding to proteins reported in scorpions from the respective family of the analyzed samples. Some of these proteins correspond to neurotoxins affecting ionic channels, antimicrobial peptides and metalloproteinase-like fragments. In the venom of Tityus asthenes, the MS n analysis allowed the detection of two toxins affecting sodium channels covering 50% and 84% of the sequence respectively, showing 100% sequence similarity. Two sequences from Tityus asthenes showed sequence similarity with a phospholipase from Opisthacanthus cayaporum indicating the presence of this type of toxin in this species for the first time. One sequence matching a hypothetical secreted protein from Hottentotta judaicus was found in three of the studied venoms. We found that this protein is common in the Buthidae family whereas it has been reported in other families - such as Scorpionidae - and may be part of the evolutionary puzzle of venoms in these arachnids. Conclusion: Buthidae venoms from Colombia can be considered an important source of peptides similar to toxins affecting ionic channels. An interesting predicted antimicrobial peptide was detected in three of the analyzed venoms.

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Section: Discussionsupporting

confidence: 59%

MS/MS analysis of four scorpion venoms from Colombia: a descriptive approach

Estrada-Gómez

Muñoz

Saldarriaga‐Córdoba

et al. 2021

J. Venom. Anim. Toxins incl. Trop. Dis

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“…To the best of our knowledge, only two peptides are known in the literature that have modulated the Kv1.5 ion current: Osu1 [91] and Ts6 [92,93]. Osu1 is a peptide isolated from the venom of a tarantula, called Oculicosa supermirabilis.…”

Section: Osu1 and Ts6: The Known Peptide Modulators Of The Kv15mentioning

confidence: 99%

Peptide Inhibitors of Kv1.5: An Option for the Treatment of Atrial Fibrillation

et al. 2021

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The human voltage gated potassium channel Kv1.5 that conducts the IKur current is a key determinant of the atrial action potential. Its mutations have been linked to hereditary forms of atrial fibrillation (AF), and the channel is an attractive target for the management of AF. The development of IKur blockers to treat AF resulted in small molecule Kv1.5 inhibitors. The selectivity of the blocker for the target channel plays an important role in the potential therapeutic application of the drug candidate: the higher the selectivity, the lower the risk of side effects. In this respect, small molecule inhibitors of Kv1.5 are compromised due to their limited selectivity. A wide range of peptide toxins from venomous animals are targeting ion channels, including mammalian channels. These peptides usually have a much larger interacting surface with the ion channel compared to small molecule inhibitors and thus, generally confer higher selectivity to the peptide blockers. We found two peptides in the literature, which inhibited IKur: Ts6 and Osu1. Their affinity and selectivity for Kv1.5 can be improved by rational drug design in which their amino acid sequences could be modified in a targeted way guided by in silico docking experiments.

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“…T . serrulatus venom has been extensively studied, mainly the sodium and potassium channel toxin [ 12 , 13 , 18 , 19 ]. Other components with low molecular mass such as hypotensins, antimicrobial peptides, bradykinin-potentiating peptides and high molecular mass such as enzymatic components like hyaluronidases, serino proteinases, metalloproteinase and proteinase inhibitors were also detected in T .…”

Section: Introductionmentioning

confidence: 99%

Proteomic endorsed transcriptomic profiles of venom glands from Tityus obscurus and T. serrulatus scorpions

et al. 2018

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BackgroundExcept for the northern region, where the Amazonian black scorpion, T. obscurus, represents the predominant and most medically relevant scorpion species, Tityus serrulatus, the Brazilian yellow scorpion, is widely distributed throughout Brazil, causing most envenoming and fatalities due to scorpion sting. In order to evaluate and compare the diversity of venom components of Tityus obscurus and T. serrulatus, we performed a transcriptomic investigation of the telsons (venom glands) corroborated by a shotgun proteomic analysis of the venom from the two species.ResultsThe putative venom components represented 11.4% and 16.7% of the total gene expression for T. obscurus and T. serrulatus, respectively. Transcriptome and proteome data revealed high abundance of metalloproteinases sequences followed by sodium and potassium channel toxins, making the toxin core of the venom. The phylogenetic analysis of metalloproteinases from T. obscurus and T. serrulatus suggested an intraspecific gene expansion, as we previously observed for T. bahiensis, indicating that this enzyme may be under evolutionary pressure for diversification. We also identified several putative venom components such as anionic peptides, antimicrobial peptides, bradykinin-potentiating peptide, cysteine rich protein, serine proteinases, cathepsins, angiotensin-converting enzyme, endothelin-converting enzyme and chymotrypsin like protein, proteinases inhibitors, phospholipases and hyaluronidases.ConclusionThe present work shows that the venom composition of these two allopatric species of Tityus are considerably similar in terms of the major classes of proteins produced and secreted, although their individual toxin sequences are considerably divergent. These differences at amino acid level may reflect in different epitopes for the same protein classes in each species, explaining the basis for the poor recognition of T. obscurus venom by the antiserum raised against other species.

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Potassium channel blockers from the venom of the Brazilian scorpion Tityus serrulatus ( )

Cited by 16 publications

References 68 publications

MS/MS analysis of four scorpion venoms from Colombia: a descriptive approach

MS/MS analysis of four scorpion venoms from Colombia: a descriptive approach

Peptide Inhibitors of Kv1.5: An Option for the Treatment of Atrial Fibrillation

Proteomic endorsed transcriptomic profiles of venom glands from Tityus obscurus and T. serrulatus scorpions

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