Molecular mechanisms of band 3 inhibitors. 3. Translocation inhibitors.

作者: Joseph J. Falke , Sunney I. Chan

DOI: 10.1021/BI00372A017

关键词: Reaction rateBiological membraneNiflumic acidStereochemistryChemistryTransmembrane domainCompartment (chemistry)Membrane transportBand 3Chromosomal translocation

摘要: During the translocation of band 3 transport site between inward- and outward-facing orientations, Cl- complex passes through a transition state lying on reaction pathway two extreme orientations. Niflumic acid, 2-[(7-nitrobenzofurazan-4-yl)amino]ethanesulfonate, 2,4,6-trichlorobenzenesulfonate each are blockers that can bind to both conformations 3. The principal mechanism these inhibitors is reduction in rate, since they have essentially no effect apparent KD for binding migration solution. Instead, raise free energy formation during thereby lock into either or orientation. In contrast, 2,4-dinitrofluorobenzene (DNFB) appears restrict accessibility solution Cl-; also, DNFB rate increased by Cl-, suggesting modification may occur translocation. Thus proposed trap Cl--transport yield conformation intermediate A model presented molecular across biological membranes. machinery contain greater than equal 6 transmembrane helices surround central channel containing sliding hydrophobic barrier. lies channel-forming remains stationary while barrier slides from one end other, exposing opposite compartment.

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