Please use this identifier to cite or link to this item:
Title: Structural characterization of myotoxic ecarpholin S from Echis carinatus venom
Authors: Zhou, X. 
Tan, T.-C.
Valiyaveettil, S. 
Mei, L.G. 
Kini, R.M. 
Velazquez-Campoy, A.
Sivaraman, J. 
Issue Date: 1-Oct-2008
Citation: Zhou, X., Tan, T.-C., Valiyaveettil, S., Mei, L.G., Kini, R.M., Velazquez-Campoy, A., Sivaraman, J. (2008-10-01). Structural characterization of myotoxic ecarpholin S from Echis carinatus venom. Biophysical Journal 95 (7) : 3366-3380. ScholarBank@NUS Repository.
Abstract: Phospholipase A2 (PLA2), a common toxic component of snake venom, has been implicated in various pharmacological effects. Ecarpholin S, isolated from the venom of the snake Echis carinatus sochureki, is a phospholipase A2 (PLA2) belonging to the Ser 49-PLA2 subgroup. It has been characterized as having low enzymatic but potent myotoxic activities. The crystal structures of native ecarpholin S and its complexes with lauric acid, and its inhibitor suramin, were elucidated. This is the first report of the structure of a member of the Ser49-PLA2 subgroup. We also examined interactions of ecarpholin S with phosphatidylglycerol and lauric acid, using surface plasmon resonance, and of suramin with isothermal titration calorimetry. Most Ca 2+-dependent PLA2 enzymes have Asp in position 49, which plays a crucial role in Ca2+ binding. The three-dimensional structure of ecarpholin S reveals a unique conformation of the Ca2+-binding loop that is not favorable for Ca2+ coordination. Furthermore, the endogenously bound fatty acid (lauric acid) in the hydrophobic channel may also interrupt the catalytic cycle. These two observations may account for the low enzymatic activity of ecarpholin S, despite full retention of the catalytic machinery. These observations may also be applicable to other non-Asp 49-PLA2 enzymes. The interaction of suramin in its complex with ecarpholin S is quite different from that reported for the Lys 49-PLA2/suramin complex, where the interfacial recognition face (i-face), C-terminal region, and N-terminal region of ecarpholin S play important roles. This study provides significant structural and functional insights into the myotoxic activity of ecarpholin S and, in general, of non-Asp49-PLA2 enzymes. © 2008 by the Biophysical Society.
Source Title: Biophysical Journal
ISSN: 00063495
DOI: 10.1529/biophysj.107.117747
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.


checked on Apr 9, 2021


checked on Apr 9, 2021

Page view(s)

checked on Apr 11, 2021

Google ScholarTM



Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.