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

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