Competitive binding of bismuth to transferrin and albumin in aqueous solution and in blood plasma.

Article Details

Citation

Sun H, Li H, Mason AB, Woodworth RC, Sadler PJ

Competitive binding of bismuth to transferrin and albumin in aqueous solution and in blood plasma.

J Biol Chem. 2001 Mar 23;276(12):8829-35. Epub 2000 Dec 7.

PubMed ID
11110794 [ View in PubMed
]
Abstract

Several bismuth compounds are currently used as antiulcer drugs, but their mechanism of action is not well established. Proteins are thought to be target sites. In this work we establish that the competitive binding of Bi(3+) to the blood serum proteins albumin and transferrin, as isolated proteins and in blood plasma, can be monitored via observation of (1)H and (13)C NMR resonances of isotopically labeled [epsilon-(13)C]Met transferrin. We show that Met(132) in the I132M recombinant N-lobe transferrin mutant is a sensitive indicator of N-lobe metal binding. Bi(3+) binds to the specific Fe(3+) sites of transferrin and the observed shifts of Met resonances suggest that Bi(3+) induces similar conformational changes in the N-lobe of transferrin in aqueous solution and plasma. Bi(3+) binding to albumin is nonspecific and Cys(34) is not a major binding site, which is surprising because Bi(3+) has a high affinity for thiolate sulfur. This illustrates that the potential target sites for metals (in this case Bi(3+)) in proteins depend not only on their presence but also on their accessibility. Bi(3+) binds to transferrin in preference to albumin both in aqueous solution and in blood plasma.

DrugBank Data that Cites this Article

Drug Carriers
DrugCarrierKindOrganismPharmacological ActionActions
Bismuth subsalicylateSerotransferrinProteinHumans
Unknown
Not AvailableDetails
Bismuth subsalicylateSerum albuminProteinHumans
No
Binder
Details