title: Mechanism of competition between chloride and stilbenedisulfonates for binding to human erythrocyte band 3 (AE1).
abstract: Stilbenedisulfonates (S) constitute an important class of competitive inhibitors of the anion exchange (AE) function found in plasma membranes of various cell types. I present a brief summary of recent kinetic studies that provide insight into the mechanism of stilbenedisulfonate-chloride competition in binding to human erythrocyte band 3 (AE1) (B), the chloride-bicarbonate exchanger. Reversible stilbenedisulfonate binding follows a two-step mechanism (S + B <--> SB <--> SB*). Several lines of evidence are summarized that show that chloride, stilbenedisulfonates, and band 3 form a ternary complex, with chloride lowering stilbenedisulfonate affinity allosterically, by accelerating the rate of stilbenedisulfonate release. Of particular significance was our evidence demonstrating that extracellular chloride could accelerate stilbenedisulfonate release from its binding site on the outer surface of band 3 in resealed ghosts (i.e., acceleration in the release of a bound competitive inhibitor by a cis substrate). I suggest that the latter result may be consistent with our earlier proposal that band 3 follows a two-site ordered sequential mechanism, where two allosterically linked chloride binding transport sites move back and forth across the membrane together.
authors.affiliation: Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198-5290, USA. jsalhan@ibm.net
authors.forename: J M
authors.initials: JM
authors.lastname: Salhany
mesh_terms: D001457:Anion Exchange Protein 1, Erythrocyte / Q000737:chemistry*; D002713:Chlorine / Q000737:chemistry*; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D011485:Protein Binding; D013050:Spectrometry, Fluorescence; D013267:Stilbenes / Q000737:chemistry*; D013997:Time Factors
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D013267:Stilbenes; D002713:Chlorine