ArticleJournal of the American Chemical Society2006
Structural and functional consequences of an amide-to-ester substitution in the selectivity filter of a potassium channel.
Article in Journal of the American Chemical Society, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Harnessing PNature communications · 2026Article
- Cloxyquin activates hTRESK by allosteric modulation of the selectivity filter.Communications biology · 2023Article
- Review
- How physical forces drive the process of helical membrane protein folding.EMBO reports · 2022Review
- Targeting the APP-Mint2 Protein-Protein Interaction with a Peptide-Based Inhibitor Reduces Amyloid-β Formation.Journal of the American Chemical Society · 2021Article
- Analysis of folded structure and folding thermodynamics in heterogeneous-backbone proteomimetics.Methods in enzymology · 2021Review
- Chemoenzymatic Semisynthesis of Proteins.Chemical reviews · 2020Review
- Chemical substitutions in the selectivity filter of potassium channels do not rule out constricted-like conformations for C-type inactivation.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Individual Ion Binding Sites in the K(+) Channel Play Distinct Roles in C-type Inactivation and in Recovery from Inactivation.Structure (London, England : 1993) · 2016Article
- Determinants of cation transport selectivity: Equilibrium binding and transport kinetics.The Journal of general physiology · 2015Review
- Isomannide-based peptidomimetics as inhibitors for human tissue kallikreins 5 and 7.ACS medicinal chemistry letters · 2014Article
- Biophysics, pathophysiology, and pharmacology of ion channel gating pores.Frontiers in pharmacology · 2014Review
- Using protein backbone mutagenesis to dissect the link between ion occupancy and C-type inactivation in K+ channels.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- An evaluation of peptide-bond isosteres.Chembiochem : a European journal of chemical biology · 2011Review
- A multipoint hydrogen-bond network underlying KcsA C-type inactivation.Biophysical journal · 2011Article
- Biological applications of protein splicing.Cell · 2010Article
- Modular strategy for the semisynthesis of a K+ channel: investigating interactions of the pore helix.ACS chemical biology · 2009Article
- Expressed protein ligation: a resourceful tool to study protein structure and function.Cellular and molecular life sciences : CMLS · 2009Review
- Unnatural amino acids: better than the real things?F1000 biology reports · 2009Article
- Chemical tools for K(+) channel biology.Biochemistry · 2009Review
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4 authors.
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Abstract
The selectivity filter of K(+) channels comprises four contiguous ion binding sites, S1 through S4. Structural and functional data indicate that the filter contains on average two K(+) ions at any given time and that these ions reside primarily in two configurations, namely to sites S1 and S3 or to sites S2 and S4. Maximum ion flux through the channel is expected to occur when the energy difference between these two binding configurations is zero. In this study, we have used protein semisynthesis to selectively perturb site 1 within the filter of the KcsA channel through use of an amide-to-ester substitution. The modification alters K(+) conduction properties. The structure of the selectivity filter is largely unperturbed by the modification, despite the loss of an ordered water molecule normally located just behind the filter. Introduction of the ester moiety was found to alter the distribution of K(+), Rb(+,) and Cs(+) within the filter, with the most dramatic change found for Rb(+). The redistribution of ions is associated with the appearance of a partially hydrated ion just external to the filter, at a position where no ion is observed in the wild-type channel. The appearance of this new ion-binding site creates a change in the distance between a pair of K(+) ions some fraction of the time, apparently leading to a reduction in the ion conduction rate. Importantly, this finding suggests that the selectivity filter of a potassium channel is optimized both in terms of absolute ion occupancy and in terms of the separation in distance between the conducting ions.
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