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Journal/Book: Proc. Natl. Acad. Sci. USA
Published: 2001
Pages: 9478–9483
Volume: 98
Issue:
Accession no.: 49
Publisher:
ISBN:

Interchain hydrogen-bonding interactions may facilitate translocation of K+ ions across the potassium channel selectivity filter, as suggested by synthetic modeling chemistry.

J. C. Mareque Rivas, H. Schwalbe, S. J. Lippard
Abstract:
A 4-fold symmetric arrangement of TVGYG polypeptides forms the selectivity filter of the K+ channel from Streptomyces lividans (KcsA). We report the synthesis and properties of synthetic models for the filter, p-tert-butyl-calix[4]arene-(OCH(2)CO-XOBz)(4) (X = V, VG, VGY), 1-3. The first cation (Na+, K+) binds to the four -[OCH(2)CO]- units, a region devised to mimic the metal-binding site formed by the four T residues in KcsA. NMR studies reveal that cations and valine amide protons compete for the carbonyl oxygen atoms, converting NH(Val)...O=C hydrogen bonds to M+ ...O=C bonds (M+ = Na+ or K+). The strength of these interchain NH(Val)...O=C hydrogen bonds varies in the order 3 > 2 > 1. We propose that such interchain H-bonding may destabilize metal binding in the selectivity filter and thus help create the low energy barrier needed for rapid cation translocation.
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Prof. Dr. Harald Schwalbe
Institut für Organische Chemie und Chemische Biologie
Johann Wolfgang Goethe Universität
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