Solvent Mediation of Peptide Conformations: Polyproline Structures in Water, Methanol, Ethanol, and 1-Propanol as Determined by Ion Mobility Spectrometry-Mass Spectrometry

El‐Baba, Tarick J.; Fuller, Daniel R.; Hales, David; Russell, David H.; Clemmer, David E.

doi:10.1007/s13361-018-2034-7

Cited by 25 publications

(35 citation statements)

References 52 publications

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“…These changes in the relative abundances of the IMS profiles as a function of the starting solvent conditions evidence that there is a "memory effect" on the observed IMS profiles despite the lasso topology, and that the organic content can significantly change the equilibria (and relative abundances) between the cis-and trans-conformers; similar trends have been previously reported in other systems [54,63]. Interestingly, changes in the TIMS distribution of the [P7A/P16A] double variant were not observed as a function of the starting solvent conditions (Figure 3b).…”

Section: Changes In Conformational Distribution As a Function Of Starting Solvent Condition And Ion Heatingsupporting

confidence: 80%

Evidence of Cis/Trans-Isomerization at Pro7/Pro16 in the Lasso Peptide Microcin J25

Fouque

Hegemann

Zirah

et al. 2019

J. Am. Soc. Mass Spectrom.

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Microcin J25 is a ribosomal synthesized and post-translationally modified peptide (RiPP) characterized by a mechanically interlocked topology called the lasso fold. This structure provides microcin J25 a potent antimicrobial activity resulting from internalization via the siderophore receptor FhuA and further inhibition of the RNA polymerase. In the present work, nuclear magnetic resonance (NMR) and trapped ion mobility spectrometry -mass spectrometry (TIMS-MS) were used to investigate the lasso structure of microcin J25. NMR experiments showed that the lasso peptide microcin J25 can adopt conformational states where Pro16 can be found in the cis-and trans-orientations. The high-resolution mobility analysis, aided by site-directed mutagenesis ([P7A], [P16A] and [P7A/P16A] variants), demonstrated that microcin J25 can adopt cis/cis-, cis/trans-, trans/cis-and trans/trans-conformations at the Pro7 and Pro16 peptide bonds. It was also shown that interconversion between the conformers can occur as a function of the starting solvent conditions and ion heating (collision induced activation, CIA) despite the lasso topology. Complementary to NMR findings, the cis-conformations at Pro7 were assigned using TIMS-MS. This study highlights the analytical power of TIMS-MS and site-directed mutagenesis for the study of biological systems with large microheterogeneity as a way to further increase our understanding of the receptor binding dynamics and biological activity.

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Section: Changes In Conformational Distribution As a Function Of Starting Solvent Condition And Ion Heatingsupporting

confidence: 80%

Evidence of Cis/Trans-Isomerization at Pro7/Pro16 in the Lasso Peptide Microcin J25

Fouque

Hegemann

Zirah

et al. 2019

J. Am. Soc. Mass Spectrom.

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“…[41][42][43] Numerous recent experimental findings of the enthalpy-entropy correlation plots for equilibrium and kinetic processes alike demonstrate that this phenomenon appears to be general-a balance that minimizes variation in free energy. 44 Additional evidence for this correlation, the enthalpy and entropy values for kinetic processes previously reported by our group for cis/trans isomerization of Pro13 and HisPro13 are also plotted in Figure 3. As with all the XPGG sequences, these other values also fall on or near the compensation line.…”

Section: Transition State Thermochemistrysupporting

confidence: 56%

Monitoring the stabilities of a mixture of peptides by mass-spectrometry-based techniques

Fuller

Conant

El‐Baba

et al. 2019

Eur J Mass Spectrom (Chichester)

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Biomolecular degradation plays a key role in proteostasis. Typically, proteolytic enzymes degrade proteins into smaller peptides by breaking amino acid bonds between specific residues. Cleavage around proline residues is often missed and requires highly specific enzymes for peptide processing due to the cyclic proline side-chain. However, degradation can occur spontaneously (i.e. in the absence of enzymes). In this study, the influence of the first residue on the stability of a series of penultimate proline containing peptides, with the sequence Xaa-Pro-Gly-Gly (where Xaa is any amino acid), is investigated with mass spectrometry techniques. Peptides were incubated as mixtures at various solution temperatures (70 C to 90 C) and were periodically sampled over the duration of the experiment. At elevated temperatures, we observe dissociation after the Xaa-Pro motif for all sequences, but at different rates. Transition state thermochemistry was obtained by studying the temperature-dependent kinetics and although all peptides show relatively small differences in the transition state free energies ($95 kJ/mol), there is significant variability in the transition state entropy and enthalpy. This demonstrates that the side-chain of the first amino acid has a significant influence on the stability of the Xaa-Pro sequence. From these data, we demonstrate the ability to simultaneously measure the dissociation kinetics and relative transition state thermochemistries for a mixture of peptides, which vary only in the identity of the N-terminal amino acid.

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“…However, as can be seen from the example presented in the preceding section, the energy difference in the molecular conformations can be significantly lower, which prevents an accurate determination of the exact multidimensional molecular structure, because the aforementioned CCS does not correspond to the real CCS. The molecular CCS reflects average values of the geometry orientation of the analyte within the whole time of measurement (May, Morris & McLean, 2017;El-Baba et al, 2018;Conant et al, 2019). However, as our research, so far, has shown, the molecular conformation and the electronic interactions can be perturbed due to solute-continuum interactions under the MS experiment.…”

Section: Discussionmentioning

confidence: 97%

A stochastic dynamic mass spectrometric diffusion method and its application to 3D structural analysis of the analytes

Ivanova

Spiteller

2019

Reviews in Analytical Chemistry

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There is a straightforward line in the recent development of the functional model connecting the experimental mass spectrometric variable intensity of a peak of an analyte ion with its thermodynamic, kinetic and diffusion parameters. It has been shown that the temporal behavior of the outcome intensity obeys a certain law: ${{\text{D}}_{{\text{SD}}}}{\text{ }} = {\text{ }}1.3193{\text{ }} \times {\text{ }}{10^{ - 14}}{\text{ }} \times {\text{ }}A{\text{ }} \times {\text{ }}{{(\overline {{I^2}} - {{(\bar I)}^2})} \over {{{(I - \bar I)}^2}}}.$ This formula is universally applicable and empirically testable and verifiable. It connects the intensity with the so-called stochastic dynamic diffusion “DSD” parameter. Its application to small-scale research, so far, using soft-ionization electrospray, atmospheric pressure chemical ionization, matrix-assisted laser desorption/ionization or collision-induced dissociation methods has shown that the DSD parameter is linearly connected with the so-called quantum chemical diffusion parameter “DQC,” obtained within Arrhenius’s theory. Therefore, the DSD parameter connects experimental measurable parameters of ions with their three-dimensional (3D) molecular and electronic structures. The corroborated empirical proof, so far, has convincingly argued that the mass spectrometry appears to be not only a robust instrumentation for highly accurate, precise and selective quantification but also is capable of providing the exact 3D molecular structure of the analytes, when it is used complementary to high accuracy methods of the computational quantum chemistry.

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Solvent Mediation of Peptide Conformations: Polyproline Structures in Water, Methanol, Ethanol, and 1-Propanol as Determined by Ion Mobility Spectrometry-Mass Spectrometry

Cited by 25 publications

References 52 publications

Evidence of Cis/Trans-Isomerization at Pro7/Pro16 in the Lasso Peptide Microcin J25

Evidence of Cis/Trans-Isomerization at Pro7/Pro16 in the Lasso Peptide Microcin J25

Monitoring the stabilities of a mixture of peptides by mass-spectrometry-based techniques

A stochastic dynamic mass spectrometric diffusion method and its application to 3D structural analysis of the analytes

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