Ligand-protein interaction in biomembrane carriers. The induced transition fit of transport catalysis.
Carrier-linked transport through biomembranes is treated under the view of catalysis. As in enzymes, substrate-protein interaction yields catalytic energy in overcoming the activation barrier. At variance with enzymes, catalytic energy is concentrated on structural changes of the carrier rather than on the substrate destabilization for facilitating the global protein rearrangements during transport. A transition state is invoked in which the binding site assumes the best fit to the substrate, whereas in the two ground (internal and external) states, the fit is poor. The maximum binding energy released in the transition state provides catalytic energy to enable the large carrier protein transformations associated with transport. This "induced transition fit" (ITF) of carrier catalysis provides a framework of rules, concerning specificity, unidirectional versus exchange type transport, directing inhibitors to the ground state instead of the transition state, and excluding simultaneous chemical and transport catalysis (vectorial group translocation). The possible role of external energy sources (ATP and Deltapsi) in supplementing the catalytic energy is elucidated. The analysis of the structure-function relationship based on new carrier structures may be challenged to account for the workings of the ITF.
Klingenberg
Martin
M
Institute of Physiological Chemistry, University of Munich, Schillerstrasse 44, 80336 Munich, Germany. klingenberg@med.uni-muenchen.de
D001665:Binding Sites; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D002384:Catalysis; D002462:Cell Membrane / Q000378:metabolism*; D004798:Enzymes / Q000737:chemistry / Q000378:metabolism*; D007425:Intracellular Membranes / Q000378:metabolism; D008024:Ligands; D008928:Mitochondria / Q000378:metabolism; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D008954:Models, Biological
D002352:Carrier Proteins; D004798:Enzymes; D008024:Ligands; D000226:Mitochondrial ADP, ATP Translocases