Effects of Alanine and Glycine Substitution for Tryptophan on the Heterogeneity of Gramicidin A Analogs in Micelles

Hinton, James F.; Washburn-McCain, A.M.; Snow, Alan D.; Douglas, James

doi:10.1006/jmre.1996.7493

Cited by 12 publications

(18 citation statements)

References 7 publications

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“…The data clearly show that gA, with four Trp residues, is more easily incorporated into bilayers (i.e., smallest DH 6 ) as single-stranded dimers than the Phe-substituted analogs. Furthermore, the results indicate that the position of the substitution also has an effect upon this incorporation; a similar type phenomenon has been observed in previous publications (Becker et al, 1991;Hinton and Washburn, 1995;Hinton et al, 1997).…”

Section: The Effects Of Trp!phe Replacements On Incorporation and Channel Lifetimesupporting

confidence: 88%

“…The goal of this research is to explain these trends using the threedimensional structures of the Phe 11 -, Phe 13 -, and Phe 15 -gA channels. A similar observation has been made elsewhere (Hinton and Washburn, 1995;Hinton et al, 1997).…”

Section: The Effects Of Trp!phe Replacements On Single-channel Conductancesupporting

confidence: 87%

“…Three-dimensional structures of native gA and its Phe 11 , Phe 13 , and Phe 15-analogs have been determined using NMR methods and DGSA. Previous research has shown that increasing the peptide/SDS ratio can induce substituted gramicidins to adopt a single helical species, enabling determination of their structures by solution NMR (Hinton and Washburn, 1995;Hinton et al, 1997). Even at the highest useable SDS concentration (;800 mM), the NOESY spectrum of Phe 9 -gA was so complex that individual species could not be defined.…”

Section: Resultsmentioning

confidence: 99%

“…Gramicidin analogs, incorporated into the SDS micelles, were first screened for structural homogeneity using methods previously published (Hinton et al, 2002;Hinton et al, 1997;Hinton and Washburn, 1995). Using nondeuterated SDS, the indole-NH NMR signals were observed for each analog.…”

Section: Sample Preparation For Structure Determination and Channel Formation Kineticsmentioning

confidence: 99%

“…Previous publications regarding the effects of amino acid replacement on the single-channel conductance and the kinetics of ion transport of certain gramicidin analogs have shown that channel function is affected to a greater extent by replacements nearer the NH 2 -terminus of the channel (Becker et al, 1991;Hinton et al, 1993Hinton et al, , 1997Hinton and Washburn, 1995;Andersen et al, 1998). Activation enthalpy is a measure of the overall energy barrier to transport of the Na 1 ions through a gramicidin channel from the binding at the channel entrance, translocation through the channel, and to the channel exit (Hinton et al, 1988b).…”

Section: The Effects Of Trp!phe Replacements On Single-channel Conductancementioning

confidence: 99%

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Effects of Phenylalanine Substitutions in Gramicidin A on the Kinetics of Channel Formation in Vesicles and Channel Structure in SDS Micelles

Jordan

Easton

Hinton

2005

Biophysical Journal

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The common occurrence of Trp residues at the aqueous-lipid interface region of transmembrane channels is thought to be indicative of its importance for insertion and stabilization of the channel in membranes. To further investigate the effects of Trp-->Phe substitution on the structure and function of the gramicidin channel, four analogs of gramicidin A have been synthesized in which the tryptophan residues at positions 9, 11, 13, and 15 are sequentially replaced with phenylalanine. The three-dimensional structure of each viable analog has been determined using a combination of two-dimensional NMR techniques and distance geometry-simulated annealing structure calculations. These phenylalanine analogs adopt a homodimer motif, consisting of two beta6.3 helices joined by six hydrogen bonds at their NH2-termini. The replacement of the tryptophan residues does not have a significant effect on the backbone structure of the channels when compared to native gramicidin A, and only small effects are seen on side-chain conformations. Single-channel conductance measurements have shown that the conductance and lifetime of the channels are significantly affected by the replacement of the tryptophan residues (Wallace, 2000; Becker et al., 1991). The variation in conductance appears to be caused by the sequential removal of a tryptophan dipole, thereby removing the ion-dipole interaction at the channel entrance and at the ion binding site. Channel lifetime variations appear to be related to changing side chain-lipid interactions. This is supported by data relating to transport and incorporation kinetics.

show abstract

Section: The Effects Of Trp!phe Replacements On Incorporation and Channel Lifetimesupporting

confidence: 88%

Section: The Effects Of Trp!phe Replacements On Single-channel Conductancesupporting

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Sample Preparation For Structure Determination and Channel Formation Kineticsmentioning

confidence: 99%

Section: The Effects Of Trp!phe Replacements On Single-channel Conductancementioning

confidence: 99%

See 3 more Smart Citations

Effects of Phenylalanine Substitutions in Gramicidin A on the Kinetics of Channel Formation in Vesicles and Channel Structure in SDS Micelles

Jordan

Easton

Hinton

2005

Biophysical Journal

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show abstract

NMR Studies of Ion-Transporting Biological Channels

Hinton

Modern Magnetic Resonance

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Molecular structure heterogeneity of gramicidin analogs incorporated into SDS micelles: a NMR study

Hinton

Jordan

Horne

2002

Journal of Molecular Structure

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Effects of Alanine and Glycine Substitution for Tryptophan on the Heterogeneity of Gramicidin A Analogs in Micelles

Cited by 12 publications

References 7 publications

Effects of Phenylalanine Substitutions in Gramicidin A on the Kinetics of Channel Formation in Vesicles and Channel Structure in SDS Micelles

Effects of Phenylalanine Substitutions in Gramicidin A on the Kinetics of Channel Formation in Vesicles and Channel Structure in SDS Micelles

NMR Studies of Ion-Transporting Biological Channels

Molecular structure heterogeneity of gramicidin analogs incorporated into SDS micelles: a NMR study

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