J Biol Chem, Vol. 274, Issue 25, 17869-17875, June 18, 1999
Binding of Nucleotide Triphosphates to Cardiotoxin Analogue II
from the Taiwan Cobra Venom (Naja naja atra)
ELUCIDATION OF THE STRUCTURAL INTERACTIONS IN THE
dATP-CARDIOTOXIN ANALOGUE II COMPLEX
Gurunathan
Jayaraman,
Thallampuranam
Krishnaswamy,
Suresh
Kumar, and
Chin
Yu
From the Department of Chemistry, National Tsing Hua University,
Hsinchu, Taiwan, Republic of China
Snake venom cardiotoxins have been recently shown
to block the enzymatic activity of phospholipid protein kinase and
Na+,K+-ATPase. To understand the
molecular basis for the inhibitory effects of cardiotoxin on the action
of these enzymes, the nucleotide triphosphate binding ability of
cardiotoxin analogue II (CTX II) from the Taiwan cobra (Naja naja
atra) venom is investigated using a variety of spectroscopic
techniques such as fluorescence, circular dichroism, and
two-dimensional NMR. CTX II is found to bind to all the four nucleotide
triphosphates (ATP, UTP, GTP, and CTP) with similar affinity. Detailed
studies of the binding of dATP to CTX II indicated that the toxin
molecule is significantly stabilized in the presence of the nucleotide.
Molecular modeling, based on the NOEs observed for the dATP·CTX II
complex, reveals that dATP binds to the CTX II molecule at the groove
enclosed between the N- and C-terminal ends of the toxin molecule.
Based on the results obtained in the present study, a molecular
mechanism to account for the inhibition of the enzymatic activity of
the phospholipid-sensitive protein kinase and
Na+,K+-ATPase is also proposed.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
