Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep25935
Title: Ringhalexin from Hemachatus haemachatus: A novel inhibitor of extrinsic tenase complex
Authors: Barnwal B. 
Jobichen C. 
Girish V.M.
Foo C.S.
Sivaraman J. 
Kini R.M. 
Keywords: anticoagulant agent
blood clotting factor 10
cancer procoagulant
cysteine proteinase
snake venom
tumor protein
amino acid sequence
animal
antagonists and inhibitors
chemically induced
chemistry
chicken
Hemachatus
human
isolation and purification
kinetics
metabolism
molecular model
mouse
paraplegia
protein secondary structure
X ray crystallography
Amino Acid Sequence
Animals
Anticoagulants
Chickens
Crystallography, X-Ray
Cysteine Endopeptidases
Factor X
Hemachatus
Humans
Kinetics
Mice
Models, Molecular
Neoplasm Proteins
Paraplegia
Protein Structure, Secondary
Snake Venoms
Issue Date: 2016
Citation: Barnwal B., Jobichen C., Girish V.M., Foo C.S., Sivaraman J., Kini R.M. (2016). Ringhalexin from Hemachatus haemachatus: A novel inhibitor of extrinsic tenase complex. Scientific Reports 6 : 25935. ScholarBank@NUS Repository. https://doi.org/10.1038/srep25935
Abstract: 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.
Source Title: Scientific Reports
URI: https://scholarbank.nus.edu.sg/handle/10635/174012
ISSN: 20452322
DOI: 10.1038/srep25935
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