The structure around the thioester bond in bovine α 2-macroglobulin : Possible implications for the conformational stability of the inhibitor on thioester cleavage

Abstract

The residues contributing to the thioester bonds in bovine α 2-macroglobulin were differentially labelled by modification of the Glu moiety with [ 14C]methylamine and of the Cys moiety with iodo[ 3H]acetate. The labelled region was identified and analyzed in a tryptic peptide. Two amino acid replacements between human and bovine α 2-macroglobulin were found at positions + 3 (Val/Ala) and + 4 (Leu/Arg) from the Glu moiety of the thioester. Thus, marked differences exist between the human and bovine proteins in side chain size and charge close to the thioester bonds. These differences may explain the greater conformational stability of bovine α 2-macroglobulin, compared with that of the human inhibitor, after cleavage of the thioester bonds.