Enzymatic repair of oxidative damage to human apolipoprotein A-I》.pdf

FEBS Letters 433 (1998) 196 200 FEBS 20670 Enzymatic repair of oxidative damage to human apolipoprotein A-I Alexander B. Sigalova,*, Lawrence J. Sternb ~Biomedieal Department, A M W Co. Ltd., 22-1-11 Tarusskaya Street, Moscow 117588, Russia bDepartment of Chemisto,, Massachusetts Institute (~f Technology, 77 Massachusetts Avenue, Cambridge, MA 02139. USA Received 22 June 1998 proteolytic susceptibility [5,8]. Recently, it has been shown Abstract Oxidative damage to apolipoprotein A-I that occurs in vivo commonly involves methionine oxidation, and is that cellular cholesterol efflux mediated by HDL depends accompanied by alterations in structure, lipid association, and upon the ratio of unoxidized/oxidized apo A-I, and that the cholesterol efflux function. We have used the enzyme peptide difference in the extent of efflux can reach 30% [9]. In addi- methionine sulfoxide reductase (PMSR) to reverse this damage, tion, Met-112 and Met-148 of apo A-I are located within the and shown by a variety of criteria that enzyme treatment restores central region of the molecule which is involved in the activa- the primary, secondary, and tertiary structure and lipid tion of the cholesterol esterifying enzyme lecithin:c