Binding of the chymotrypsin substrate, tryptophan methyl ester, by rat α-fetoprotein

Abstract

We studied how tryptophan methyl ester and related compounds inhibit binding of estrone to rat α-fetoprotein and find that: (a) like chymotrypsin, α-fetoprotein binds tryptophan esters with higher affinity than tryptophan or its amides; (b) the affinity of α-fetoprotein for tryptophan methyl ester is 3.7 · 10 −4 M, which is close to the affinity of chymotrypsin (10 −4 M); (c) α-fetoprotein binding of tryptophan methyl ester is stereoselective and pH dependent. All of these observations suggest that there is a specific interaction between α-fetoprotein and the chymotrypsin substrate, tryptophan methyl ester, and that rat α-fetoprotein contains a site with some structural similarities to the catalytic site in chymotrypsin. Since we also find that tryptophan methyl ester is a competitive inhibitor of estrone binding to α-fetoprotein, it is possible that the protease substrate binding site on α-fetoprotein is spatially close to the estrone binding site.