A highly reactive tyrosine residue as part of the indole and benzodiazepine binding site of human serum albumin

Involvement of tyrosyl residues in the binding of benzodiazepines to their brain receptors

“…It is plausible to assume that the modified tyrosine is exposed to the outer surface of the receptor since N-acetylimidazole was reported not to react with buried tyrosine residues [5]. In [1], a tyrosine residue was reported to be involved in the binding of benzodiazepines and indoles, e.g., L-tryptophan, to human serum albumin, and evidence was also that in the latter macromolecule the nitrated amino acid is not tryptophan. The similarity between the binding sites of serum albumin and brain benzodiazepine receptors is limited, since the affinity of benzodiazepines to brain receptors is several orders of magnitude higher than their affinity for serum albumin, and the binding of [3H] FNZ to calf brain receptor is not displaced even by 10 -2 M L-tryptophan.…”

“…No information is yet available on the identity of amino acid residues in the binding site(s) of brain benzodiazepine receptors. Evidence was provided in [ 1 ] for the involvement ofa tyrosyl residue in the binding of indoles and benzodiazepines to human serum albumin. It is thus pertinent to investigate whether tyrosine also plays a role in the binding of benzodiazepines to their brain receptors.…”

The role of albumin conformation in the binding of diazepam to human serum albumin

“…It has been established that the binding of the anticoagulant drug warfarin to albumin * is affected by this N-B transition [2]. Miiller and WoUert [8], Fehske et al [9], Brodersen et al [10] and Sudlow et al [11] have demonstrated at least two very specific and selective binding sites to be present on the albumin molecule for a large number of highly bound drugs. These sites are the so-called warfarin and diazepam binding site, also denoted as site I and site II by Sudlow et al [11].…”

The fatty-acid-induced conformational states of human serum albumin investigated by means of multiple co-binding of protons and oleic acid

“…(1) Albumin has two specific binding sites, the diazepam-and the warfarin-binding site (Sudlow et al, 1976;Brodersen et al, 1977;Fehske et al, 1979Fehske et al, , 1981Sjoholm et al, 1979), also called 'site II' and 'site I' repectively.…”

“…Reaction 4 has also been studied recently by measuring the free concentration of drug as a function of the ratio of F and as a function of pH (Droge et al, 1985). In (Fehske et al, 1981) and a site-II drug (diazepam) (Sudlow et al, 1976;Brodersen et al, 1977;Fehske et al, 1979Fehske et al, , 1981 are used as a label.…”