Abstract
Snake venoms are rich sources of biologically active proteins and polypeptides. Three-finger toxins are non-enzymatic proteins present in elapid (cobras, kraits, mambas and sea snakes) and colubrid venoms. These proteins contain four conserved disulfide bonds in the core to maintain the three-finger folds. Although all three-finger toxins have similar fold, their biological activities are different. A new three-finger toxin (hemachatoxin) was isolated from Hemachatus haemachatus (Ringhals cobra) venom. Its amino acid sequence was elucidated, and crystal structure was determined at 2.43 Å resolution. The overall fold is similar to other three-finger toxins. The structure and sequence analysis revealed that the fold is maintained by four highly conserved disulfide bonds. It exhibited highest similarity to particularly P-type cardiotoxins that are known to associate and perturb the membrane surface with their lipid binding sites. Also, the increased B value of hemachotoxin loop II suggests that loop II is flexible and may remain flexible until its interaction with membrane phospholipids. Based on the analysis, we predict hemachatoxin to be cardiotoxic/cytotoxic and our future experiments will be directed to characterize the activity of hemachatoxin.
Highlights
Snake venoms are rich sources of biologically active proteins and polypeptides [1]
Some of the well characterized superfamilies of snake venom proteins include three-finger toxins (3FTxs), C-type lectin like proteins (CLPs), phospholipase A2s (PLA2s), serine proteases and metalloproteases [4,5,6]. 3FTxs, nonenzymatic snake venom proteins, are the most abundant toxins found in elapid and colubrid venoms [4,7]
The three-finger fold is observed in various other proteins like xenoxins from X. laevis [34] and HEP21 from hen egg white [35], as well as mammalian Ly-6 alloantigens [36], urokinase-plasminogen activator receptor [37] and complement regulatory protein CD59 [38]. 3FTxs in snake venoms are thought to be evolved from non-toxic ancestral proteins through gene duplication and accelerated evolution [39,40]
Summary
Snake venoms are rich sources of biologically active proteins and polypeptides [1]. Apart from its crucial role in paralyzing and digesting prey, snake venom is an excellent source for novel toxins. Snake venom toxins can be broadly categorized as enzymatic and non-enzymatic proteins They are classified into various toxin superfamilies. Based on their biological properties, 3FTxs can be classified as postsynaptic neurotoxins targeting the nicotinic [23] and muscarinic [24] acetylcholine receptors, cardiotoxins/cytotoxins targeting phospholipid membranes [25], fasciculins targeting acetylcholinesterase (AChE) [26], calciseptins and FS2 toxins targeting L-type calcium channels [27,28], anticoagulants like naniproin, exactin and siamextin [R. The three-finger fold is observed in various other proteins like xenoxins from X. laevis [34] and HEP21 from hen egg white [35], as well as mammalian Ly-6 alloantigens [36], urokinase-plasminogen activator receptor [37] and complement regulatory protein CD59 [38]. 3FTxs in snake venoms are thought to be evolved from non-toxic ancestral proteins through gene duplication and accelerated evolution [39,40]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
