Mechanistic basis for site-site interactions in inhibitor and substrate binding to band 3 (AE1): evidence distinguishing allosteric from electrostatic effects.
Kinetic studies suggest that stilbenedisulfonates inhibit erythrocyte anion exchange by competing with substrate anions for binding to band 3 (AE1). Such competition seems to involve site-site interactions between distinct inhibitor and substrate binding sites. The molecular basis for site-site interactions could be allosteric or electrostatic. In this paper, inhibitor binding kinetic studies are reviewed, and 35Cl(-) NMR line-broadening experiments are presented, both of which seem to rule out an electrostatic hypothesis. The results are consistent with an allosteric site-site interaction mechanism in the binding of stilbenedisulfonate and substrate anions to band 3.
Salhany
J M
JM
Veterans Administration Medical Center, University of Nebraska Medical Center, Omaha, Nebraska 68198-5290, USA. jsalhan@attglobal.net
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D000495:Allosteric Site; D001457:Anion Exchange Protein 1, Erythrocyte / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D002712:Chlorides; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D013379:Substrate Specificity
D001457:Anion Exchange Protein 1, Erythrocyte; D002712:Chlorides; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid