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Title: Structural and Pharmacological Comparison of Daboiatoxin from Badoia russelli siamensis with Viperotoxing F and Vipoxin from Other Vipers

Abstract

Russell's viper (Vipera russelli, also known as Daboia russelli) is one of the major causes of fatal snakebites. To date, five Daboia russelli subspecies have been recognized. Daboiatoxin (DbTx) is the main lethal phospholipase A{sub 2} (PLA{sub 2}) toxin in the venom of D. russelli siamensis (Myanmar viper) and has strong neurotoxic, myotoxic and cytotoxic activities. DbTx and its homologous neurotoxins viperotoxin F from D. russelli formosensis (Taiwan viper) and vipoxin from the Bulgarian sand viper V. ammodytes meridionalis consist of complexes between a nontoxic acidic PLA2 protein and an enzymatically active basic PLA2. DbTx and viperotoxin F are presynaptic toxins, while vipoxin is postsynaptic. The two chains of DbTx have been separated and their PLA2 enzymatic activity has been measured using the secretory PLA2 assay kit. The enzymatic activity of DbTx chain B is reduced by 30% of its original activity by chain A in a unimolar ratio, thus indicating that DbTx chain A acts as an inhibitor. The lethal activity of the two chains has also been studied in male albino mice and chain A is less lethal than chain B. The crystal structure of DbTx has also been determined and its structural details are compared with thosemore » of the two homologues. Furthermore, an attempt is made to correlate the sequence and structural determinants of these toxins with their enzymatic activities and their pharmacological effects.« less

Authors:
; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL) National Synchrotron Light Source
Sponsoring Org.:
Doe - Office Of Science
OSTI Identifier:
930448
Report Number(s):
BNL-81200-2008-JA
Journal ID: ISSN 0907-4449; TRN: US200904%%720
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta Crystallographica Section D: Biological Crystallography; Journal Volume: 63
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; CRYSTAL STRUCTURE; ENZYME IMMUNOASSAY; ENZYMES; MICE; PROTEINS; SNAKES; STRUCTURAL CHEMICAL ANALYSIS; TOXINS; VENOMS; national synchrotron light source

Citation Formats

Gopolan,G., Thwin, M., Gopalakrishnakone, P., and Swaminathan, K.. Structural and Pharmacological Comparison of Daboiatoxin from Badoia russelli siamensis with Viperotoxing F and Vipoxin from Other Vipers. United States: N. p., 2007. Web. doi:10.1107/S0907444907016204.
Gopolan,G., Thwin, M., Gopalakrishnakone, P., & Swaminathan, K.. Structural and Pharmacological Comparison of Daboiatoxin from Badoia russelli siamensis with Viperotoxing F and Vipoxin from Other Vipers. United States. doi:10.1107/S0907444907016204.
Gopolan,G., Thwin, M., Gopalakrishnakone, P., and Swaminathan, K.. Mon . "Structural and Pharmacological Comparison of Daboiatoxin from Badoia russelli siamensis with Viperotoxing F and Vipoxin from Other Vipers". United States. doi:10.1107/S0907444907016204.
@article{osti_930448,
title = {Structural and Pharmacological Comparison of Daboiatoxin from Badoia russelli siamensis with Viperotoxing F and Vipoxin from Other Vipers},
author = {Gopolan,G. and Thwin, M. and Gopalakrishnakone, P. and Swaminathan, K.},
abstractNote = {Russell's viper (Vipera russelli, also known as Daboia russelli) is one of the major causes of fatal snakebites. To date, five Daboia russelli subspecies have been recognized. Daboiatoxin (DbTx) is the main lethal phospholipase A{sub 2} (PLA{sub 2}) toxin in the venom of D. russelli siamensis (Myanmar viper) and has strong neurotoxic, myotoxic and cytotoxic activities. DbTx and its homologous neurotoxins viperotoxin F from D. russelli formosensis (Taiwan viper) and vipoxin from the Bulgarian sand viper V. ammodytes meridionalis consist of complexes between a nontoxic acidic PLA2 protein and an enzymatically active basic PLA2. DbTx and viperotoxin F are presynaptic toxins, while vipoxin is postsynaptic. The two chains of DbTx have been separated and their PLA2 enzymatic activity has been measured using the secretory PLA2 assay kit. The enzymatic activity of DbTx chain B is reduced by 30% of its original activity by chain A in a unimolar ratio, thus indicating that DbTx chain A acts as an inhibitor. The lethal activity of the two chains has also been studied in male albino mice and chain A is less lethal than chain B. The crystal structure of DbTx has also been determined and its structural details are compared with those of the two homologues. Furthermore, an attempt is made to correlate the sequence and structural determinants of these toxins with their enzymatic activities and their pharmacological effects.},
doi = {10.1107/S0907444907016204},
journal = {Acta Crystallographica Section D: Biological Crystallography},
number = ,
volume = 63,
place = {United States},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}
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