Fifty Years of Animal Toxin Research at the Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry RAS

Abstract

This review covers briefly the work carried out at our institute (IBCh), in many cases in collaboration with other Russian and foreign laboratories, for the last 50 years. It discusses the discoveries and studies of various animal toxins, including protein and peptide neurotoxins acting on the nicotinic acetylcholine receptors (nAChRs) and on other ion channels. Among the achievements are the determination of the primary structures of the α-bungarotoxin-like three-finger toxins (TFTs), covalently bound dimeric TFTs, glycosylated cytotoxin, inhibitory cystine knot toxins (ICK), modular ICKs, and such giant molecules as latrotoxins and peptide neurotoxins from the snake, as well as from other animal venoms. For a number of toxins, spatial structures were determined, mostly by 1H-NMR spectroscopy. Using this method in combination with molecular modeling, the molecular mechanisms of the interactions of several toxins with lipid membranes were established. In more detail are presented the results of recent years, among which are the discovery of α-bungarotoxin analogs distinguishing the two binding sites in the muscle-type nAChR, long-chain α-neurotoxins interacting with α9α10 nAChRs and with GABA-A receptors, and the strong antiviral effects of dimeric phospholipases A2. A summary of the toxins obtained from arthropod venoms includes only highly cited works describing the molecules’ success story, which is associated with IBCh. In marine animals, versatile toxins in terms of structure and molecular targets were discovered, and careful work on α-conotoxins differing in specificity for individual nAChR subtypes gave information about their binding sites.

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

“…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 ].…”

“…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 ]. In this paper, the structure–function relationships in CTs will be considered.…”