J Biol Chem, Vol. 275, Issue 2, 983-991, January 14, 2000
Functional Characteristics of a Phospholipase A2
Inhibitor from Notechis ater Serum*
Peter G.
Hains,
Kah-Leong
Sung,
Albert
Tseng, and
Kevin W.
Broady
From the Toxin Research Group, Department of Cell and Molecular
Biology, University of Technology, Westbourne St., Gore Hill,
Sydney 2065, Australia
A phospholipase A2 inhibitor
has been purified from the serum of Notechis ater using
DEAE-Sephacel chromatography. The inhibitor was found to be composed of
two protein subunits (
and 
) that form the intact complex of
approximately 110 kDa. The -chain is a 30-kDa glycoprotein and the
-chain a nonglycosylated, 25-kDa protein. N-terminal sequence
analysis reveals a high level of homology to other snake phospholipase
A2 inhibitors. The inhibitor was shown to be extremely pH
and temperature stable. The inhibitor was tested against a wide variety
of phospholipase A2 enzymes and inhibited the enzymatic
activity of all phospholipase A2 enzymes tested, binding
with micromole to nanomole affinity. Furthermore, the inhibitor was
compared with the Eli-Lilly compound LY311727 and found to have a
higher affinity for human secretory nonpancreatic phospholipase
A2 than this chemical inhibitor. The role of the carbohydrate moiety was investigated and found not to affect the in vitro function of the inhibitor.
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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