期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 97, 期 8, 页码 3959-3964出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.97.8.3959
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In this study, the charge selectivity of staphylococcal alpha-hemolysin (alpha HL), a bacterial pore-forming toxin, is manipulated by using cyclodextrins as noncovalent molecular adapters. Anion-selective versions of alpha HL, including the wild-type pore and various mutants, become more anion selective when beta-cyclodextrin (beta CD) is lodged within the channel lumen. By contrast, the negatively charged adapter, hepta-6-sulfato-beta-cyclodextrin (s(7)beta CD), produces cation selectivity. The cyclodextrin adapters have similar effects when placed in cation-selective mutant alpha HL pores. Most probably, hydrated Cl- ions partition into the central cavity of beta CD more readily than K+ ions, whereas s(7)beta CD introduces a charged ring near the midpoint of the channel lumen and confers cation selectivity through electrostatic interactions. The molecular adapters generate permeability ratios (PK+/PCl-) over a 200-fold range and should be useful in the de novo design of membrane channels both for basic studies of ion permeation and for applications in biotechnology.
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