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PhTX-II a basic myotoxic phospholipase A₂ from Porthidium hyoprora snake venom, pharmacological characterization and amino acid sequence by mass spectrometry.
- Source :
-
Toxins [Toxins (Basel)] 2014 Oct 31; Vol. 6 (11), pp. 3077-97. Date of Electronic Publication: 2014 Oct 31. - Publication Year :
- 2014
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Abstract
- A monomeric basic PLA₂ (PhTX-II) of 14149.08 Da molecular weight was purified to homogeneity from Porthidium hyoprora venom. Amino acid sequence by in tandem mass spectrometry revealed that PhTX-II belongs to Asp49 PLA₂ enzyme class and displays conserved domains as the catalytic network, Ca²⁺-binding loop and the hydrophobic channel of access to the catalytic site, reflected in the high catalytic activity displayed by the enzyme. Moreover, PhTX-II PLA₂ showed an allosteric behavior and its enzymatic activity was dependent on Ca²⁺. Examination of PhTX-II PLA₂ by CD spectroscopy indicated a high content of alpha-helical structures, similar to the known structure of secreted phospholipase IIA group suggesting a similar folding. PhTX-II PLA₂ causes neuromuscular blockade in avian neuromuscular preparations with a significant direct action on skeletal muscle function, as well as, induced local edema and myotoxicity, in mice. The treatment of PhTX-II by BPB resulted in complete loss of their catalytic activity that was accompanied by loss of their edematogenic effect. On the other hand, enzymatic activity of PhTX-II contributes to this neuromuscular blockade and local myotoxicity is dependent not only on enzymatic activity. These results show that PhTX-II is a myotoxic Asp49 PLA₂ that contributes with toxic actions caused by P. hyoprora venom.
- Subjects :
- Acetophenones therapeutic use
Amino Acid Sequence
Animals
Calcium Chelating Agents pharmacology
Catalytic Domain
Chickens
Conserved Sequence
Crotalid Venoms antagonists & inhibitors
Crotalid Venoms toxicity
Edema etiology
Edema prevention & control
Enzyme Inhibitors pharmacology
Enzyme Inhibitors therapeutic use
Group II Phospholipases A2 chemistry
Group II Phospholipases A2 isolation & purification
Group II Phospholipases A2 metabolism
In Vitro Techniques
Mice
Molecular Sequence Data
Muscle, Skeletal pathology
Muscle, Skeletal physiopathology
Myositis prevention & control
Neurotoxins antagonists & inhibitors
Neurotoxins chemistry
Neurotoxins isolation & purification
Sequence Alignment
Sequence Homology, Amino Acid
Snake Bites drug therapy
Snake Bites pathology
Viperidae
Crotalid Venoms enzymology
Disease Models, Animal
Group II Phospholipases A2 toxicity
Muscle, Skeletal drug effects
Myositis etiology
Neurotoxins toxicity
Snake Bites physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 2072-6651
- Volume :
- 6
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Toxins
- Publication Type :
- Academic Journal
- Accession number :
- 25365526
- Full Text :
- https://doi.org/10.3390/toxins6113077