Three finger toxins of elapids: structure, function, clinical applications and its inhibitors

Hiremath, Kashinath; Dodakallanavar, Jagadeesh; Sampat, Ganesh H.; Patil, Vishal S.; Harish, Darasaguppe R.; Chavan, Rajashekar; Hegde, Harsha V.; Roy, Subarna

doi:10.1007/s11030-023-10734-3

Cited by 1 publication

(1 citation statement)

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“…Among the variety of non-enzymatic toxins present in the venoms of various organisms, toxins with a three-finger structure (TFT) play a prominent role [ 1 , 2 , 3 , 4 , 5 ]. Among TFTs, there are toxins, e.g., neurotoxins (NTs) of narrowly targeted action that interact with protein receptors [ 5 , 6 , 7 , 8 , 9 ]. Other representatives of TFTs, cytotoxins (CT), or cardiotoxins interact with a wider range of biomolecules, which include primarily lipids as well as, at least, carbohydrates and proteins [ 9 , 10 , 11 , 12 ].…”

Section: Introductionmentioning

confidence: 99%

Specific Amino Acid Residues in the Three Loops of Snake Cytotoxins Determine Their Membrane Activity and Provide a Rationale for a New Classification of These Toxins

Dubovskii,

Utkin

2024

Toxins

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Cytotoxins (CTs) are three-finger membrane-active toxins present mainly in cobra venom. Our analysis of the available CT amino acid sequences, literature data on their membrane activity, and conformational equilibria in aqueous solution and detergent micelles allowed us to identify specific amino acid residues which interfere with CT incorporation into membranes. They include Pro9, Ser28, and Asn/Asp45 within the N-terminal, central, and C-terminal loops, respectively. There is a hierarchy in the effect of these residues on membrane activity: Pro9 > Ser28 > Asn/Asp45. Taking into account all the possible combinations of special residues, we propose to divide CTs into eight groups. Group 1 includes toxins containing all of the above residues. Their representatives demonstrated the lowest membrane activity. Group 8 combines CTs that lack these residues. For the toxins from this group, the greatest membrane activity was observed. We predict that when solely membrane activity determines the cytotoxic effects, the activity of CTs from a group with a higher number should exceed that of CTs from a group with a lower number. This classification is supported by the available data on the cytotoxicity and membranotropic properties of CTs. We hypothesize that the special amino acid residues within the loops of the CT molecule may indicate their involvement in the interaction with non-lipid targets.

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