The features of the spatial structure of the gramicidine A‐cesium complex

Nekrasov, A. N.; Stepanov, A. V.; Timofeev, Vladimir P.

doi:10.1016/0014-5793(95)00800-o

Cited by 8 publications

(10 citation statements)

References 11 publications

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“…Chemically, the presence of anions within the channels of both the Cs ϩ and K ϩ structures is anomalous since the single-valency cation selectivity of gramicidin is well established. 31,32,36 Similarly, there appears to be no reason for Cs ϩ to bind external to the channel as found in the previously published model. 40 More troubling are the crystallographic anomalies that appear to be present.…”

Section: Figure 10supporting

confidence: 67%

“…24 It has been proposed that tryptophan conformations and conformational changes are specifically correlated with gramicidin orientation in and association with membrane lipids, ion coordination, and bilayer ion transport. [25][26][27][28][29][30][31][32][33][34][35][36] The tryptophan residues at 9, 11, 13, and 15 differ significantly with respect to these properties in both single-and doublestranded dimer models. 26 Studies of naturally occurring and synthetic isomers indicate that amino acid variation at position 11, in particular, has significant effects on channel opening, duration, and transport properties.…”

Section: Introductionmentioning

confidence: 99%

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Gramicidin D conformation, dynamics and membrane ion transport

et al. 1999

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The linear pentadecapeptide antibiotic, gramicidin D, a heterogeneous mixture of six components, is a naturally occurring product of Bacillus brevis known to form ion channels in synthetic and natural membranes. The conformation of gramicidin A in the solid state, in organic solvents, and in planar lipid bilayers and the relationship between the composition and the conformation of gramicidin and its selective transport of ions across membranes has been the subject of intense investigation for over 50 years. The x‐ray crystal structure and nmr solution spectroscopy agree fully with one another and reveal that entirely different conformations of gramicidin are present in uncomplexed and ion complexed forms. Precise refinements of the three‐dimensional structures of naturally occurring gramicidin D in crystals obtained from methanol, ethanol, and n‐propanol demonstrate the unexpected presence of stable left‐handed antiparallel double‐helical heterodimers that vary with the crystallization solvent. The side chains of Trp residues in the three structures exhibit sequence‐specific patterns of conformational preference. Tyr substitution for Trp at position 11 appears to favor β ribbon formation and stabilization of the antiparallel double helix. This conformation acts as a template for gramicidin folding and nucleation of the different crystal forms. The fact that a minor component in a heterogeneous mixture influences aggregation and crystal nucleation has potential applications to other systems in which anomalous behavior is exhibited by aggregation of apparently homogeneous materials, such as the enigmatic behavior of prion proteins. The crystallographically determined structures of cesium, potassium, rubidium, and hydronium ion complexes of gramicidin A are in excellent agreement with the nmr structure determination of the cesium ion gramicidin complex in a methanol chloroform mixture (50 : 50). The right‐handed antiparallel double stranded double helical structures (DSDHR) also exhibit geometric features compatible with the solid‐state 15N and 2H nmr data recorded for gramicidin in planar lipid bilayers and attributed to the active form of gramicidin A. The DSDHRcrystal structures reveal an ion channel with a single partially solvated cation distributed over three ion binding sites. The channel lumen is relatively smooth and electrostatically negative as required for cation passage, while the exterior is electrostatically neutral, a requirement for membrane insertion. The “coordination” of the Cs+ion is achieved by interaction with the π orbitals of the carbonyls which do not point toward the ions. The K+ binding sites, which are similar in position to Cs+ binding sites, are shifted off center slightly toward the wall of the channel. © 1999 John Wiley & Sons, Inc. Biopoly 51: 129–144, 1999

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Section: Figure 10supporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Gramicidin D conformation, dynamics and membrane ion transport

et al. 1999

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“…Both structures demonstrate a new fold, a right-handed double-stranded antiparallel double helix (DSDH ) form, that is consistent with most of the existing literature on gramicidin structure, ion conductance, and side-chain interactions including a previously published solution NMR structure of a Cs ϩ complexed gramicidin (12). More importantly, the structures demonstrate a remarkable similarity with the solid-state NMR data of gramicidin in oriented bilayers (11).…”

supporting

confidence: 68%

The conducting form of gramicidin A is a right-handed double-stranded double helix

Burkhart

Langs

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

123

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The linear pentadecapeptide antibiotic, gramicidin D, is a naturally occurring product of Bacillus brevis known to form ion channels in synthetic and natural membranes. The x-ray crystal structures of the right-handed double-stranded double-helical dimers (DSDH ) reported here agree with 15 N-NMR and CD data on the functional gramicidin D channel in lipid bilayers. These structures demonstrate single-file ion transfer through the channels. The results also indicate that previous crystal structure reports of a left-handed double-stranded double-helical dimer in complex with Cs ؉ and K ؉ salts may be in error and that our evidence points to the DSDH as the major conformer responsible for ion transport in membranes.

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“…DCLs templated with CsCl and NH 4 SCN (Table 1, entries 7 and 8) resulted in formation of the antiparallel dimer 2–3 as the dominant product (amplification factor=4). These results suggest that Cs + and NH 4 + cations preferentially stabilize the antiparallel arrangement, which is in agreement with the ds ↑↓ β‐helical folding reported for gA in solution14, 15j and the solid state15e, k in the presence of CsCl. However, these structures differed in their handedness and periodicity.…”

Section: Resultssupporting

confidence: 90%

Dynamic Combinatorial Enrichment of Polyconformational D‐/L‐Peptide Dimers

Jadhav

Lichtenecker

Bullach

et al. 2015

Chemistry A European J

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D-/L-peptides such as gramicidin A (gA) adopt unique dimeric β-helical structures of different topologies. To overcome their conformational promiscuity and enrich individual components, a dynamic combinatorial approach assisted by thiol tags was developed. This method led to identification of the preferential formation of antiparallel dimers under a broad range of conditions, which was independent of peptide side-chain polarity. Exclusive formation of an antiparallel cyclic dimer was achieved in the presence of cesium ions.

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The features of the spatial structure of the gramicidine A‐cesium complex

Cited by 8 publications

References 11 publications

Gramicidin D conformation, dynamics and membrane ion transport

Gramicidin D conformation, dynamics and membrane ion transport

The conducting form of gramicidin A is a right-handed double-stranded double helix

Dynamic Combinatorial Enrichment of Polyconformational D‐/L‐Peptide Dimers

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