PMID:17325012
| Citation |
Naftalin, RJ, Green, N and Cunningham, P (2007) Lactose permease H+-lactose symporter: mechanical switch or Brownian ratchet? Biophys. J. 92:3474-91 |
|---|---|
| Abstract |
Lactose permease structure is deemed consistent with a mechanical switch device for H(+)-coupled symport. Because the crystallography-assigned docking position of thiodigalactoside (TDG) does not make close contact with several amino acids essential for symport; the switch model requires allosteric interactions between the proton and sugar binding sites. The docking program, Autodock 3 reveals other lactose-docking sites. An alternative cotransport mechanism is proposed where His-322 imidazolium, positioned in the central pore equidistant (5-7 A) between six charged amino acids, Arg-302 and Lys-319 opposing Glu-269, Glu-325, Asp-237, and Asp-240, transfers a proton transiently to an H-bonded lactose hydroxyl group. Protonated lactose and its dissociation product H(3)O+ are repelled by reprotonated His-322 and drift in the electrostatic field toward the cytosol. This Brownian ratchet model, unlike the conventional carrier model, accounts for diminished symport by H322N mutant; how H322 mutants become uniporters; why exchanging Lys-319 with Asp-240 paradoxically inactivates symport; how some multiple mutants become revertant transporters; the raised export rate and affinity toward lactose of uncoupled mutants; the altered specificity toward lactose, melibiose, and galactose of some mutants, and the proton dissociation rate of H322 being 100-fold faster than the symport turnover rate. |
| Links |
PubMed PMC1853157 Online version:10.1529/biophysj.106.100669 |
| Keywords |
Binding Sites; Biomechanics; Computer Simulation; Diffusion; Enzyme Activation; Escherichia coli Proteins/chemistry; Escherichia coli Proteins/ultrastructure; Lactose/chemistry; Models, Chemical; Models, Molecular; Molecular Motor Proteins/chemistry; Molecular Motor Proteins/ultrastructure; Monosaccharide Transport Proteins/chemistry; Monosaccharide Transport Proteins/ultrastructure; Protein Binding; Protein Conformation; Protons; Substrate Specificity; Symporters/chemistry; Symporters/ultrastructure; Water/chemistry |
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