Ts8

• Comment: I am no expert, but it looks like Tityustoxin is the same substance? If so, please expand the existing article. If it is a separate topic, please explain on the talk page and I will re-review. Curb Safe Charmer (talk) 13:35, 25 October 2022 (UTC)

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Ts8 (also known as) TsK2; Tityustoxin K-beta; TsTX-K beta and TsTx-Kβ) is a neurotoxin present in the venom of the Brazilian yellow scorpion, Tityus serrulatus. Ts8 targets voltage-gated potassium channels, by selective inhibition of the Kv4.2 channels.

Etymology

The neurotoxin Ts8 is derived from the Brazillian yellow scorpion, Tityus serrulatus (Ts). Alternative names for the Ts8 toxin are TsK2, Tityustoxin K-, TsTX-Kβ and TsTx-Kβ.

Sources

The Ts8 neurotoxin can be derived from the venom of the Brazilian yellow scorpion, Tityus serrulatus. The Tityus serrulatus is found predominantly in Brazil.

Chemistry

Ts8 belongs to the β-KTx family 1. Toxins in this family contain about 59-75 amino acid residues and three disulfide bridges. There are two-domain peptides; the N-terminal helical domain (NHD) and the C-terminal CSαβ domain (CCD). CCD stands for neurotoxic activity and this activity in Ts8 concludes that this toxin is very selective for Kv4.2 channels. The neurotoxin Ts8 itself contains 60 amino acid residues and the three disulfide bridges that were mentioned. It has a molecular weight of 6716 Da. The sequence of the amino acids is as followed:

K-L-V-A-L-I-P-N-D-Q-L-R-S-I-L-K-A-V-V-H-K-V-A-K-T-Q-F-G-C-P-A-Y-E-G-Y-C-N-D-H-C-N-D-I-E-R-K-D-G-E-C-H-G-F-K-C-K-C-A-K-D

Physical and chemical characteristics of Ts8

Molecular weight	Amino acids
6716 Da	60

Target

The main targets of Ts8 are the Kv-channels, particularly the Kv4.2 channel. The Kv4.2 channel is part of the Kv channels family of voltage-gated ion channels, consisting of at least eleven subfamilies. Ts8 selectively inhibits Kv4.2 Channel. The inhibition is completely reversible. Although Ts8 selectively inhibits the Kv4.2 channel it never inhibits 100% of the peak current, even with high concentrations. Kv4.2 channels are found in a variety of tissues, including high levels in the brain and heart.

When treating Ts8 with recombinant purification and mass spectrometry analysis, it showed that there are three recombinant forms. The recombinant Ts8-FragII is reported to have a small inhibitory effect on the Kv1.3 channel.

Mode of action

The inhibition caused by the neurotoxin Ts8 on Kv4.2 channels increased with time. This increase falls together with the inactivation rate of the channels, which also increased. These two increases could indicate that the toxin has a preference to bind to the inactivated state of the Kv4.2 channels. Furthermore, Ts8 does not induce pore-forming activity.

Toxicity

The LD50 of the Ts8 toxin is unknown. Ts8 is known to selectively inhibit the Kv4.2 channels, with a maximal blocking effect of 65% in mice. In Mice, Ts8 increases earlier nociception with higher doses. Elimination or inhibition of Kv4.2 channels via intraplantar injections was seen to induce hypersensitivity to mechanical stimuli. Via intrathecal injection this effect was prolonged and a prolongation plateau of mechanical hypersensitivity was observed. Thus Ts8 can enhance sensitivity to tactile- and mechanical stimuli in mice, by inhibition of the Kv4.2 channels. The symptoms caused by Ts8 induce hyperalgesia, intense and persistent pain.

In human erythrocytes, the hemolytic action of the neurotoxin Ts8 was tested. Here they tested Ts8 in a dilution series with concentration between 0.04 - 46.21 µM. Here they discovered that Ts8 is toxic to human erythrocytes type A+ in concentrations above 2.89 µM.

Treatment

A sting by Tityus serrulatus is treated with a scorpion antivenom serum. This serum, Soro antiscorpionico, containing a human antibody fragment, neutralizes most of the entire venomous cocktail of neurotoxins. Information on how to treat Ts8 is unknown.

Therapeutic use

In a study from Cordeiro et al (2022) they expressed recombinant Ts8 (rTs8) in Pichia pastoris yeast to be able to evaluate the peptide expression under different conditioning. They looked at the native Ts8 and recombinant Ts8, rTs8-FragI and rTs8-FragII. These forms were all evaluated by an antimicrobial assay. This resulted in the growth inhibition of Pichia pastoris. The native form of the toxin had a larger inhibition effect than the recombinant forms.

The study from Oliveira et al (2022) showed the antimicrobial activity of Ts8. Here they tested the native Ts8 against different types of microorganisms;

• Gram-positive bacteria: Micrococcus luteus
• Gram-negative bacteria: Eschericha coli
• Yeast: Candida albicans
• Filamentous fungus: Aspergillus niger

Ts8 had antimicrobial activity for all of these named microorganisms. Ts8 has the strongest effect on  the gram-negative bacteria, and the lowest effect on both the yeast and the filamentous fungus. This testing was an initial screening to be able to expand the spectrum of action of this toxin. As mentioned before, Ts8 can be toxic for human erythrocytes. The concentration of the antimicrobial assay on Eschericha coli is lower than what is toxic for the human erythrocytes, 1.45 µM. Thus it can be concluded that Ts8 hypothetically can be used as an antibiotic against Eschericha coli, but with care.