title: Inhibition of 3,5,3'-triiodothyronine binding to its receptor in rat liver by protease inhibitors and substrates.
abstract: Various protease inhibitors (e.g. phenylmethanesulfonyl fluoride (PMSF), tosyl-phenylalanine chloromethyl ketone (TosPheCH2Cl)) and substrates (e.g., tosyl-arginine methyl ester (TosArgOMe), tryptophan methyl ester (TrpOMe)) inhibit the binding of adrenal and sex steroids to their cognate receptors (Hubbard and Kalimi (1985) Mol. Cell. Biochem. 66, 101-109). Here we extend this finding to the receptor for 3,5,3'-triiodothyronine (T3) in rat liver nuclei. We find that PMSF, TosPheCH2Cl and other protease inhibitors as well as TosArgOMe, TrpOMe, tyrosine methyl ester (TyrOMe) and tyrosine ethyl ester (TyrOEt) inhibit binding of 125I-T3 to its receptor in rat liver nuclei. Inhibition by protease substrates appears to be at or close to the hormone binding domain. By analogy with the known mechanism of binding of protease inhibitors and substrates to enzymes, we suggest that the T3 receptor contains a nucleophilic site at or close to the hormone binding domain.
authors.affiliation: Institute of Experimental Endocrinology, Slovak Academy of Sciences, Bratislava.
authors.forename: J
authors.initials: J
authors.lastname: Brtko
authors.forename: J
authors.initials: J
authors.lastname: Knopp
authors.forename: M E
authors.initials: ME
authors.lastname: Baker
mesh_terms: D000818:Animals; D008099:Liver / Q000378:metabolism; D008297:Male; D015394:Molecular Structure; D010664:Phenylmethylsulfonyl Fluoride / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000494:pharmacology; D014106:Tosylarginine Methyl Ester / Q000494:pharmacology; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014284:Triiodothyronine / Q000378:metabolism*; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D011480:Protease Inhibitors; D011988:Receptors, Thyroid Hormone; D013450:Sulfones; D014284:Triiodothyronine; C040444:tyrosine methyl ester; C002010:4-(2-aminoethyl)benzenesulfonylfluoride; D014108:Tosylphenylalanyl Chloromethyl Ketone; D014443:Tyrosine; D010664:Phenylmethylsulfonyl Fluoride; C028129:tryptophan methyl ester; D014364:Tryptophan; D014106:Tosylarginine Methyl Ester