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Snake Venom Cytotoxins, Phospholipase A2s, and Zn(2+)-dependent Metalloproteinases: Mechanisms of Action and Pharmacological Relevance.

Gasanov SE, Dagda RK, Rael ED - J Clin Toxicol (2014)

Bottom Line: We also propose biomedical applications whereby snake venom toxins can be employed for treating human diseases.Additionally, increasing our understanding of the molecular mechanism(s) by which snake venom PLA2s promote hydrolysis of cell membrane phospholipids can give insight into the underlying biomedical implications for treating autoimmune disorders that are caused by dysregulated endogenous PLA2 activity.Lastly, we provide an exhaustive overview of snake venom Zn(2+)-dependent metalloproteinases and suggest ways by which these enzymes can be engineered for treating deep vein thrombosis and neurodegenerative disorders.

View Article: PubMed Central - PubMed

Affiliation: Applied Mathematics and Informatics Department, Moscow State University Branch, 22 A. Timur Avenue, Tashkent 100060, Uzbekistan ; Science Department, Tashkent Ulugbek International School, 5-A J. Shoshiy Street, Tashkent 100100, Uzbekistan.

ABSTRACT
Snake venom toxins are responsible for causing severe pathology and toxicity following envenomation including necrosis, apoptosis, neurotoxicity, myotoxicity, cardiotoxicity, profuse hemorrhage, and disruption of blood homeostasis. Clinically, snake venom toxins therefore represent a significant hazard to snakebite victims which underscores the need to produce more efficient anti-venom. Some snake venom toxins, however, have great potential as drugs for treating human diseases. In this review, we discuss the biochemistry, structure/function, and pathology induced by snake venom toxins on human tissue. We provide a broad overview of cobra venom cytotoxins, catalytically active and inactive phospholipase A2s (PLA2s), and Zn(2+)-dependent metalloproteinases. We also propose biomedical applications whereby snake venom toxins can be employed for treating human diseases. Cobra venom cytotoxins, for example, may be utilized as anti-cancer agents since they are efficient at destroying certain types of cancer cells including leukemia. Additionally, increasing our understanding of the molecular mechanism(s) by which snake venom PLA2s promote hydrolysis of cell membrane phospholipids can give insight into the underlying biomedical implications for treating autoimmune disorders that are caused by dysregulated endogenous PLA2 activity. Lastly, we provide an exhaustive overview of snake venom Zn(2+)-dependent metalloproteinases and suggest ways by which these enzymes can be engineered for treating deep vein thrombosis and neurodegenerative disorders.

No MeSH data available.


Related in: MedlinePlus

A rendering of the 3D structure of cardiotoxin III from Naja naja atraA ribbon diagram of the crystal structure of cardiotoxin III (PDB #2CRT) is illustrated to highlight the hydrophobic core region and show basic residues in blue and acidic residues in red. Right panel: A rendering of the Coloumbic electrostatic field potential map for cardiotoxin III which shows that the toxin possesses a very extensive and wide basic electrostatic field potential landscape (blue). Electrostatic field potential calculations, 3D molecular rendering, and specific annotations of cardiotoxin III was performed by using the Swiss PDB Viewer software.
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Figure 1: A rendering of the 3D structure of cardiotoxin III from Naja naja atraA ribbon diagram of the crystal structure of cardiotoxin III (PDB #2CRT) is illustrated to highlight the hydrophobic core region and show basic residues in blue and acidic residues in red. Right panel: A rendering of the Coloumbic electrostatic field potential map for cardiotoxin III which shows that the toxin possesses a very extensive and wide basic electrostatic field potential landscape (blue). Electrostatic field potential calculations, 3D molecular rendering, and specific annotations of cardiotoxin III was performed by using the Swiss PDB Viewer software.

Mentions: Cytotoxins contain approximately 60 amino acid residues (~7 kDa) and are structurally characterized by the presence of the three-fingered (TF) fold (Figure 1). The β-strands of the antiparallel β-sheet give rise to the hydrophobic core of the molecule, hence the name of the TF fold. All cobra venom cytotoxins have a similar 3D structure stabilized by four disulfide bonds. Cytotoxins exhibit strong amphiphilic properties on their molecular surface: apolar tips of loops I–III that form a hydrophobic core flanked by a positively charged “ring” composed mostly of conserved Lys and Arg residues that are clustered near the N-terminal region of the protein and by a less polar C-terminal region (Figure 1). In general, most cytotoxins are highly positively charged molecules that have very extensive basic electrostatic field potential maps.


Snake Venom Cytotoxins, Phospholipase A2s, and Zn(2+)-dependent Metalloproteinases: Mechanisms of Action and Pharmacological Relevance.

Gasanov SE, Dagda RK, Rael ED - J Clin Toxicol (2014)

A rendering of the 3D structure of cardiotoxin III from Naja naja atraA ribbon diagram of the crystal structure of cardiotoxin III (PDB #2CRT) is illustrated to highlight the hydrophobic core region and show basic residues in blue and acidic residues in red. Right panel: A rendering of the Coloumbic electrostatic field potential map for cardiotoxin III which shows that the toxin possesses a very extensive and wide basic electrostatic field potential landscape (blue). Electrostatic field potential calculations, 3D molecular rendering, and specific annotations of cardiotoxin III was performed by using the Swiss PDB Viewer software.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4060629&req=5

Figure 1: A rendering of the 3D structure of cardiotoxin III from Naja naja atraA ribbon diagram of the crystal structure of cardiotoxin III (PDB #2CRT) is illustrated to highlight the hydrophobic core region and show basic residues in blue and acidic residues in red. Right panel: A rendering of the Coloumbic electrostatic field potential map for cardiotoxin III which shows that the toxin possesses a very extensive and wide basic electrostatic field potential landscape (blue). Electrostatic field potential calculations, 3D molecular rendering, and specific annotations of cardiotoxin III was performed by using the Swiss PDB Viewer software.
Mentions: Cytotoxins contain approximately 60 amino acid residues (~7 kDa) and are structurally characterized by the presence of the three-fingered (TF) fold (Figure 1). The β-strands of the antiparallel β-sheet give rise to the hydrophobic core of the molecule, hence the name of the TF fold. All cobra venom cytotoxins have a similar 3D structure stabilized by four disulfide bonds. Cytotoxins exhibit strong amphiphilic properties on their molecular surface: apolar tips of loops I–III that form a hydrophobic core flanked by a positively charged “ring” composed mostly of conserved Lys and Arg residues that are clustered near the N-terminal region of the protein and by a less polar C-terminal region (Figure 1). In general, most cytotoxins are highly positively charged molecules that have very extensive basic electrostatic field potential maps.

Bottom Line: We also propose biomedical applications whereby snake venom toxins can be employed for treating human diseases.Additionally, increasing our understanding of the molecular mechanism(s) by which snake venom PLA2s promote hydrolysis of cell membrane phospholipids can give insight into the underlying biomedical implications for treating autoimmune disorders that are caused by dysregulated endogenous PLA2 activity.Lastly, we provide an exhaustive overview of snake venom Zn(2+)-dependent metalloproteinases and suggest ways by which these enzymes can be engineered for treating deep vein thrombosis and neurodegenerative disorders.

View Article: PubMed Central - PubMed

Affiliation: Applied Mathematics and Informatics Department, Moscow State University Branch, 22 A. Timur Avenue, Tashkent 100060, Uzbekistan ; Science Department, Tashkent Ulugbek International School, 5-A J. Shoshiy Street, Tashkent 100100, Uzbekistan.

ABSTRACT
Snake venom toxins are responsible for causing severe pathology and toxicity following envenomation including necrosis, apoptosis, neurotoxicity, myotoxicity, cardiotoxicity, profuse hemorrhage, and disruption of blood homeostasis. Clinically, snake venom toxins therefore represent a significant hazard to snakebite victims which underscores the need to produce more efficient anti-venom. Some snake venom toxins, however, have great potential as drugs for treating human diseases. In this review, we discuss the biochemistry, structure/function, and pathology induced by snake venom toxins on human tissue. We provide a broad overview of cobra venom cytotoxins, catalytically active and inactive phospholipase A2s (PLA2s), and Zn(2+)-dependent metalloproteinases. We also propose biomedical applications whereby snake venom toxins can be employed for treating human diseases. Cobra venom cytotoxins, for example, may be utilized as anti-cancer agents since they are efficient at destroying certain types of cancer cells including leukemia. Additionally, increasing our understanding of the molecular mechanism(s) by which snake venom PLA2s promote hydrolysis of cell membrane phospholipids can give insight into the underlying biomedical implications for treating autoimmune disorders that are caused by dysregulated endogenous PLA2 activity. Lastly, we provide an exhaustive overview of snake venom Zn(2+)-dependent metalloproteinases and suggest ways by which these enzymes can be engineered for treating deep vein thrombosis and neurodegenerative disorders.

No MeSH data available.


Related in: MedlinePlus