Identification of Arginine Residues in Peptides by 2D-IR Echo Spectroscopy

Ghosh, Ayanjeet; Tucker, Matthew J.; Hochstrasser, Robin M.

doi:10.1021/jp201794n

Cited by 45 publications

(74 citation statements)

References 41 publications

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“…At pH 7.0, in the closed state, both Ala30 and Gly34 in the drug free channel exhibit very slow spectral diffusion dynamics, indicating that the water structure near these sites is more ordered or even "frozen" on the timescale of our experiments, similar to that observed in ice crystals. 57 This is consistent with our prior experiments 33 and also MD simulations. 22,23 However, upon binding of a drug the water dynamics inside the channel become distinctively faster, as manifested by the faster spectral diffusion times of Al30 and Gly34.…”

Section: Probing Water Dynamics Through Amide Frequency Relaxationssupporting

confidence: 91%

“…A recent 2D IR study 33 has shown that energy transfer between two degenerate CN stretching modes of the guanidyl side chain of arginine, the infrared transitions of which overlap spectrally with isotopically edited amides, can occur on the timescale of a few picoseconds. Moreover, the carboxylate sidechains of glutamic and aspartic acids also absorb in the same spectral range as isotopically labeled amide modes.…”

Section: Mutation Of the M2 Sequencementioning

confidence: 99%

“…Interestingly, such an asymmetry was not observed in our prior experiments, where the occurrence of a doublet was attributed to separate conformers of the channel. 33 Thus, the possibility of the doublet arising from structural asymmetry that is inherent to the R45A mutant and not to the wild type cannot be ruled out.…”

Section: Solvent Exchange Between Amide Sites Exposes Drug-water Imentioning

confidence: 99%

“…When used in conjunction with isotope labeling, one can obtain residue-by-residue information on hydration dynamics, as has been demonstrated with experiment and theory over the past decade on several membrane protein domains, including CD3zeta, M2, and ovispirin. [29][30][31][32] In this study, we use a double mutant (D44N, R45A) 31,33,34 of the transmembrane domain of the M2 channel, with the pore lining carbonyls of its Ala30 and Gly34 residues isotopically labeled (i.e., 12 C= 16 O to 13 C= 18 O) to serve as site-specific IR probes. [35][36][37][38] The use of this double mutant avoids any potential complexity arising from the 2D IR signals of arginine and aspartic acid, which overlap with those of the 13 C= 18 O groups.…”

Section: Introductionmentioning

confidence: 99%

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2D IR spectroscopy reveals the role of water in the binding of channel-blocking drugs to the influenza M2 channel

Ghosh

Wang

Moroz

et al. 2014

The Journal of Chemical Physics

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Water is an integral part of the homotetrameric M2 proton channel of the influenza A virus, which not only assists proton conduction but could also play an important role in stabilizing channel-blocking drugs. Herein, we employ two dimensional infrared (2D IR) spectroscopy and site-specific IR probes, i.e., the amide I bands arising from isotopically labeled Ala30 and Gly34 residues, to probe how binding of either rimantadine or 7,7-spiran amine affects the water dynamics inside the M2 channel. Our results show, at neutral pH where the channel is non-conducting, that drug binding leads to a significant increase in the mobility of the channel water. A similar trend is also observed at pH 5.0 although the difference becomes smaller. Taken together, these results indicate that the channel water facilitates drug binding by increasing its entropy. Furthermore, the 2D IR spectral signatures obtained for both probes under different conditions collectively support a binding mechanism whereby amantadine-like drugs dock in the channel with their ammonium moiety pointing toward the histidine residues and interacting with a nearby water cluster, as predicted by molecular dynamics simulations. We believe these findings have important implications for designing new anti-influenza drugs. © 2014 AIP Publishing LLC. [http://dx

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Section: Probing Water Dynamics Through Amide Frequency Relaxationssupporting

confidence: 91%

Section: Mutation Of the M2 Sequencementioning

confidence: 99%

Section: Solvent Exchange Between Amide Sites Exposes Drug-water Imentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

2D IR spectroscopy reveals the role of water in the binding of channel-blocking drugs to the influenza M2 channel

Ghosh

Wang

Moroz

et al. 2014

The Journal of Chemical Physics

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“…30 Here, these factors are assumed to only occur during the waiting time T. The S H T G n (ω, T) terms in Eq. (10) correspond to the individual Liouville pathway diagrams 30 such that,…”

Section: E Population Transfermentioning

confidence: 99%

Vibrational dynamics of a non-degenerate ultrafast rotor: The (C12,C13)-oxalate ion

Kuroda

Abdo

Chuntonov

et al. 2013

The Journal of Chemical Physics

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Molecular ions undergoing ultrafast conformational changes on the same time scale of water motions are of significant importance in condensed phase dynamics. However, the characterization of systems with fast molecular motions has proven to be both experimentally and theoretically challenging. Here, we report the vibrational dynamics of the non-degenerate (C12,C13)-oxalate anion, an ultrafast rotor, in aqueous solution. The infrared absorption spectrum of the (C12,C13)-oxalate ion in solution reveals two vibrational transitions separated by approximately 40 cm −1 in the 1500-1600 cm −1 region. These two transitions are assigned to vibrational modes mainly localized in each of the carboxylate asymmetric stretch of the ion. Two-dimensional infrared spectra reveal the presence and growth of cross-peaks between these two transitions which are indicative of coupling and population transfer, respectively. A characteristic time of sub-picosecond cross-peaks growth is observed. Ultrafast pump-probe anisotropy studies reveal essentially the same characteristic time for the dipole reorientation. All the experimental data are well modeled in terms of a system undergoing ultrafast population transfer between localized states. Comparison of the experimental observations with simulations reveal a reasonable agreement, although a mechanism including only the fluctuations of the coupling caused by the changes in the dihedral angle of the rotor, is not sufficient to explain the observed ultrafast population transfer.

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Protein–excipient interactions: Mechanisms and biophysical characterization applied to protein formulation development

Kamerzell¹,

Esfandiary²,

Joshi³

et al. 2011

Advanced Drug Delivery Reviews

426

347

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Identification of Arginine Residues in Peptides by 2D-IR Echo Spectroscopy

Cited by 45 publications

References 41 publications

2D IR spectroscopy reveals the role of water in the binding of channel-blocking drugs to the influenza M2 channel

2D IR spectroscopy reveals the role of water in the binding of channel-blocking drugs to the influenza M2 channel

Vibrational dynamics of a non-degenerate ultrafast rotor: The (C12,C13)-oxalate ion

Protein–excipient interactions: Mechanisms and biophysical characterization applied to protein formulation development

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