tailieunhanh - Báo cáo khoa học: An asymmetric ion channel derived from gramicidin A Synthesis, function and NMR structure

The biological ion channel gramicidin A (gA) was modified by synthetic means to obtain the tail-to-tail linked asymmetric gA-derived dimer com-pound3. Single-channel current measurements for 3in planar lipid bilayers exhibit an Eisenman I ion selectivity for alkali cations. The structural asymmetry does not lead to an observable functional asymmetry. The structure of 3in solution without and with Cs cations was investigated by 1 H-NMR spectroscopy. In CDCl3 ⁄CD3OH (1 : 1, v⁄v),3forms a mixture of double-strandedb-helices | ềFEBS Journal An asymmetric ion channel derived from gramicidin A Synthesis function and NMR structure Xiulan Xie1 Lo ay Al-Momani1 Philipp ReiB1 Christian Griesinger2 and Ulrich Koert1 1 Fachbereich Chemie Philipps-Universitat Marburg Germany 2 Max-Planck Institut fur Biophysikalische Chemie Gottingen Germany Keywords asymmetric D L-peptides CD spectroscopy DYANA NMR structure ion channel b-helix Correspondence U. Koert Fachbereich Chemie Philipps-Universitat Marburg Hans-Meerwein-Strasse 35032 Marburg Germany Fax 49 6421 282 5677 Tel 49 6421 282 6970 E-mail koert@ Received 1 October 2004 revised 16 November 2004 accepted 16 December 2004 doi The biological ion channel gramicidin A gA was modified by synthetic means to obtain the tail-to-tail linked asymmetric gA-derived dimer compound 3. Single-channel current measurements for 3 in planar lipid bilayers exhibit an Eisenman I ion selectivity for alkali cations. The structural asymmetry does not lead to an observable functional asymmetry. The structure of 3 in solution without and with Cs cations was investigated by 1H-NMR spectroscopy. In CDCl3 CD3OH 1 1 v v 3 forms a mixture of double-stranded b-helices. Upon addition of excess CsCl the doublestranded species are converted completely into one new conformer the right-handed single-stranded b-helix. A combination of DQF-COSY and TOCSY was used for the assignment of the 1H-NMR spectrum of the Cs-3 complex in CDCl3 CD3OH 1 1 v v . A total of 69 backbone 27 long-range and 64 side-chain distance restraints were obtained from NOESY together with 25 and 14 Xi torsion angles obtained from coupling constants. These data were used as input for structure calculation with DYANA built in SYBYL . A final set of 11 structures with an average rmsd for the backbone of A was obtained PDB 1TKQ . The structure of the Cs-3 complex in solution is equivalent to the bioactive channel conformation in the membrane environment. .

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