Identification and Structural Characterization of a New Three-Finger Toxin Hemachatoxin from Hemachatus haemachatus Venom

Girish, Vallerinteavide Mavelli; Kumar, Srinivasan Dinesh; Joseph, Lissa; Jobichen, Chacko; Kini, R. Manjunatha; Sivaraman, J.

doi:10.1371/journal.pone.0048112

Cited by 21 publications

(12 citation statements)

References 84 publications

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“…Hemachatoxin is a P-type CT isolated and crystallized from Hemacatus hemacatus venom. It has been suggested that loop II of this toxin is highly flexible [ 90 ].…”

Section: Snake Venom Peptides and Their Potential Pharmacological mentioning

confidence: 99%

Snake Venom Peptides: Tools of Biodiscovery

Munawar

Ali

Akrem

et al. 2018

Toxins

113

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Nature endowed snakes with a lethal secretion known as venom, which has been fine-tuned over millions of years of evolution. Snakes utilize venom to subdue their prey and to survive in their natural habitat. Venom is known to be a very poisonous mixture, consisting of a variety of molecules, such as carbohydrates, nucleosides, amino acids, lipids, proteins and peptides. Proteins and peptides are the major constituents of the dry weight of snake venoms and are of main interest for scientific investigations as well as for various pharmacological applications. Snake venoms contain enzymatic and non-enzymatic proteins and peptides, which are grouped into different families based on their structure and function. Members of a single family display significant similarities in their primary, secondary and tertiary structures, but in many cases have distinct pharmacological functions and different bioactivities. The functional specificity of peptides belonging to the same family can be attributed to subtle variations in their amino acid sequences. Currently, complementary tools and techniques are utilized to isolate and characterize the peptides, and study their potential applications as molecular probes, and possible templates for drug discovery and design investigations.

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“…Hemachatoxin is a P-type CT isolated and crystallized from Hemacatus hemacatus venom. It has been suggested that loop II of this toxin is highly flexible [ 90 ].…”

Section: Snake Venom Peptides and Their Potential Pharmacological mentioning

confidence: 99%

Snake Venom Peptides: Tools of Biodiscovery

Munawar

Ali

Akrem

et al. 2018

Toxins

113

View full text Add to dashboard Cite

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“… ( A ) Sequence alignment of ringhalexin and its homologs, bucain [2H8U] 64 , α-bungarotoxin [1HC9] 65 , hemachatoxin [3VTS] 66 , cardiotoxin V [1KXI] 67 , muscarinic toxin MT1[4DO8] 68 , ρ-Da1a toxin [4IYE] 69 and cardiotoxin A3 [2BHI] 70 . This figure was generated using the programs ClustalW 71 .…”

Section: Figurementioning

confidence: 99%

Ringhalexin from Hemachatus haemachatus: A novel inhibitor of extrinsic tenase complex

Barnwal

Jobichen

Girish

et al. 2016

Sci Rep

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Anticoagulant therapy is used for the prevention and treatment of thromboembolic disorders. Blood coagulation is initiated by the interaction of factor VIIa (FVIIa) with membrane-bound tissue factor (TF) to form the extrinsic tenase complex which activates FX to FXa. Thus, it is an important target for the development of novel anticoagulants. Here, we report the isolation and characterization of a novel anticoagulant ringhalexin from the venom of Hemachatus haemachatus (African Ringhals Cobra). Amino acid sequence of the protein indicates that it belongs to the three-finger toxin family and exhibits 94% identity to an uncharacterized Neurotoxin-like protein NTL2 from Naja atra. Ringhalexin inhibited FX activation by extrinsic tenase complex with an IC50 of 123.8 ± 9.54 nM. It is a mixed-type inhibitor with the kinetic constants, Ki and Ki’ of 84.25 ± 3.53 nM and 152.5 ± 11.32 nM, respectively. Ringhalexin also exhibits a weak, irreversible neurotoxicity on chick biventer cervicis muscle preparations. Subsequently, the three-dimensional structure of ringhalexin was determined at 2.95 Å resolution. This study for the first time reports the structure of an anticoagulant three-finger toxin. Thus, ringhalexin is a potent inhibitor of the FX activation by extrinsic tenase complex and a weak, irreversible neurotoxin.

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“…Mostly, 3FTxs exist as monomers, e.g. fulgimotoxin from green vine snake Oxybelis fulgidus , candoxin from Malayan krait Bungarus candidus , denmotoxin, from Boiga dendrophila (mangrove catsnake) , β‐cardiotoxin from Ophiophagus hannah , hemachatoxin (P‐type cardiotoxin) from Hemachatus hemachatus venom . However, dimeric 3FTxs are also reported, e.g.…”

Section: Introductionmentioning

confidence: 99%

Purification and Characterization of Nk‐3FTx: A Three Finger Toxin from the Venom of North East Indian Monocled Cobra

Das

Sharma

Das

et al. 2015

J Biochem & Molecular Tox

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Snake venom three finger toxins (3FTxs) are a non-enzymatic family of venom proteins abundantly found in elapids. We have purified a 7579.5 ± 0.591 Da 3FTx named as Nk-3FTx from the venom of Naja kaouthia of North East India origin. The primary structure was determined by a combination of N-terminal sequencing and electrospray ionization liquid chromatography-mass spectrometry/mass spectrometry. Biochemical and biological characterization reveal that it is nontoxic to human cell lines and exhibit mild anticoagulant activity when tested on citrated human plasma. Nk-3FTx was found to affect the compound action potential (CAP) and nerve conduction velocity of isolated toad sciatic nerve. This is the first report of a non-conventional 3FTx from Naja kaouthia venom that reduces CAP for its neurotoxic effect. Further studies can be carried out to understand the mechanism of action and to explore its potential therapeutic application.

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Identification and Structural Characterization of a New Three-Finger Toxin Hemachatoxin from Hemachatus haemachatus Venom

Cited by 21 publications

References 84 publications

Snake Venom Peptides: Tools of Biodiscovery

Snake Venom Peptides: Tools of Biodiscovery

Ringhalexin from Hemachatus haemachatus: A novel inhibitor of extrinsic tenase complex

Purification and Characterization of Nk‐3FTx: A Three Finger Toxin from the Venom of North East Indian Monocled Cobra

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