L. Ding et al., BIOCHEMICAL-CHARACTERIZATION OF SELENIUM-CONTAINING CATALYTIC ANTIBODY AS A CYTOSOLIC GLUTATHIONE-PEROXIDASE MIMIC, Biochemical journal, 332, 1998, pp. 251-255
A selenium-containing catalytic antibody (Se-4A4), prepared by convert
ing reactive serine residues of a monoclonal antibody (4A4) raised aga
inst a GSH derivative into selenocysteines, acts as a mimic of cytosol
ic glutathione peroxidase (cGPX). To clarify the mechanism of action o
f this catalytic antibody, detailed studies on kinetic behaviour and b
iological activity were carried out. A rate of acceleration (k(cat)/K-
m/k(uncat)) 10(7)-fold that of the uncatalytic reaction is observed. U
nder similar conditions, the turnover number (k(cat)) of Se-4A4 is 42%
of that of the natural rabbit liver cGPX. The Se-4A4 reaction involve
s a Ping Pong mechanism, which is the same as that of the natural cGPX
. The selenocysteine residue is located in the binding site of the ant
ibody and is shown to be crucial for this activity. Of the thiol compo
unds tested, only GSH is able to serve as substrate for Se-4A4. It was
demonstrated, using the free-radical-damage system (hypoxanthine/xant
hine oxidase) of cardiac mitochondria, that Se-4A4 can protect mitocho
ndria from free-radical damage at least 10(4)-fold more effectively th
an the natural cGPX.