BIOCHEMICAL-CHARACTERIZATION OF SELENIUM-CONTAINING CATALYTIC ANTIBODY AS A CYTOSOLIC GLUTATHIONE-PEROXIDASE MIMIC

Citation
L. Ding et al., BIOCHEMICAL-CHARACTERIZATION OF SELENIUM-CONTAINING CATALYTIC ANTIBODY AS A CYTOSOLIC GLUTATHIONE-PEROXIDASE MIMIC, Biochemical journal, 332, 1998, pp. 251-255
Citations number
35
Categorie Soggetti
Biology
Journal title
ISSN journal
02646021
Volume
332
Year of publication
1998
Part
1
Pages
251 - 255
Database
ISI
SICI code
0264-6021(1998)332:<251:BOSCA>2.0.ZU;2-T
Abstract
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.