Ion-molecule reactions as probes of gas-phase structures of peptides and proteins

Green, M. Kirk; Lebrilla, Carlito B.

doi:10.1002/(sici)1098-2787(1997)16:2<53::aid-mas1>3.0.co;2-8

Cited by 237 publications

(229 citation statements)

References 105 publications

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“…H/D exchange of small ions with a variety of reagents has received considerable attention [16,41,42]. Mechanisms associated with larger systems are less clear; however, several models have been proposed [16,19] (For a recent review of ion-molecule reactions as probes of gas-phase conformation also see [13]). Beauchamp and coworkers have previously proposed that H/D exchange between small peptide oligomers and D 2 O proceeds via a relay mechanism involving complexes where the D 2 O interacts through hydrogen bonds at two sites on the peptide [16].…”

Section: Assessing the Number Of Exchangeable Hydrogens On A Calculatmentioning

confidence: 99%

Temperature-dependent H/D exchange of compact and elongated cytochrome c ions in the gas phase

Valentine

Clemmer

2002

J. Am. Soc. Mass Spectrom.

109

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Isotopic exchange reactions of compact and elongated conformations of gaseous cytochrome c ions (ϩ5 and ϩ9 states) with D 2 O have been measured as a function of temperature (from 300 to ϳ440 K) using ion mobility techniques. Rate constants for those sites that exchange at high temperatures (Ͼ400 K) are about an order of magnitude smaller than rate constants for sites that exchange at 300 K. Although the exchange rates decrease, the maximum exchange levels for rapidly exchanging sites increase with temperature. At 300 K, exchange levels of 53 Ϯ 3 and 63 Ϯ 3 are measured for the compact and elongated states, respectively. From 300 to 335 K, the exchange levels increase slightly to ϳ60 to 70 hydrogens. Above 335 K, the levels increase to a value of ϳ200 for the ϩ5 state and ϳ190 for the ϩ9 state, near the maximum possible levels, 200 and 204 for these respective charge states. Molecular dynamics simulations have been carried out on structures having calculated cross sections that are near the experimental values in order to explore the exchange process. Overall, it appears that charge site and exchange site proximities are important factors in the exchange profiles for the elongated ϩ9 ion and the compact ϩ5 ion. (J Am Soc Mass Spectrom 2002, 13, 506 -517) © 2002 American Society for Mass Spectrometry I t is well known that the structures of proteins are influenced by environmental factors such as solution composition, pH, and temperature. However, the degree to which environment and intrinsic properties influence structure is not well understood. Structural domains such as ␣-helices, which are stable in a wide range of environments, were predicted theoretically without considering effects of solvation [1]. More subtle features, such as tertiary structure in different environments, are difficult to predict. Recently, efforts have been made to gather information about the degree to which solvent-free protein conformations resemble their native solution structures [2]. Several studies of lyophilized protein powders have shown that removal of solvent can cause structural changes [3], and the extent of differences between lyophilized and solution states is an active area [4]. New ion sources [5,6] make it possible to isolate biomolecules in the gas phase as ions, and a number of mass spectrometry (MS) based strategies for examining solvent-free conformations are being developed . The new information from these technologies is beginning to be evaluated by theoretical methods [33, 34,35]. There is now substantial evidence that, under some experimental conditions, anhydrous protein and peptide ions may retain elements of solution conformation.The conformations of cytochrome c ions have been examined previously by a number of MS techniques [8, 28]. Ion mobility (for reviews of ion mobility studies see [30]) and isotopic exchange studies [7-10, 11, 12] provide information about the overall shape and number of accessible exchange sites, respectively. These studies indicate the presence of multiple conformations within ind...

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Section: Assessing the Number Of Exchangeable Hydrogens On A Calculatmentioning

confidence: 99%

Temperature-dependent H/D exchange of compact and elongated cytochrome c ions in the gas phase

Valentine

Clemmer

2002

J. Am. Soc. Mass Spectrom.

109

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“…6 The gas-phase H/D exchange studies may give relative exchange rates for different reaction sites, [6][7][8] location of the charge, 7,8 and dependence on the deuterating agent. 6,8 Histidine is one of the 20 naturally occurring R-amino acids. It serves inter alia as a precursor of the hormone histamine, and it regulates the proper utilization of the trace metals and is essential in their rapid excretion, if they were present in excessive amounts.…”

Section: Introductionmentioning

confidence: 99%

Gas-Phase Structure of Protonated Histidine and Histidine Methyl Ester: Combined Experimental Mass Spectrometry and Theoretical ab Initio Study

et al. 2005

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Gas-phase H/D exchange experiments with CD 3 OD and D 2 O and quantum chemical ab initio G3(MP2) calculations were carried out on protonated histidine and protonated histidine methyl ester in order to elucidate their bonding and structure. The H/D exchange experiments show that both ions have three equivalent fast hydrogens and one appreciably slower exchangeable hydrogen assigned to the protonated amino group participating in a strong intramolecular hydrogen bond (IHB) with the nearest N(sp 2 ) nitrogen of the imidazole fragment and to the distal ring NH-group, respectively. It is taken for granted that the proton exchange in the IHB is much faster than the H/D exchange. Unlike in other protonated amino acids (glycine, proline, phenylalanine, tyrosine, and tryptophan) studied earlier, the exchange rate of the carboxyl group in protonated histidine is slower than that of the amino group. The most stable conformers and the enthalpies of neutral and protonated histidine and its methyl ester are calculated at the G3(MP2) level of theory. It is shown that strong intramolecular hydrogen bonding between the amino group and the imidazole ring nitrogen sites is responsible for the stability and specific properties of the protonated histidine. It is found that the proton fluctuates between the amino and imidazole groups in the protonated form across an almost vanishing barrier. Proton affinity (PA) of histidine calculated by the G3(MP2) method is 233.2 and 232.4 kcal mol -1 for protonation at the imidazole ring and at the amino group nitrogens, respectively, which is about 3-5 kcal mol -1 lower than the reported experimental value.

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“…H /D exchange (HDX) is one of the most popular techniques for the structural elucidation of biomolecules in mass spectrometry and has been widely implemented for both solution [1][2][3][4] and gas phase studies [5][6][7][8][9][10][11][12][13][14][15][16][17][18]. In solution, the extent of HDX can be directly related to the solvent accessibility of amino acid residues in proteins.…”

mentioning

confidence: 99%

“…However, in the gas phase there are many structural parameters apart from the surface availability that affect the HDX rates, as illustrated in a recent HDX study on ion-mobilityselected charge states of bovine ubiquitin [17]. Systematic studies on small peptide systems showed that the difference in proton affinity of the biomolecules and deuterated donor reagent plays a crucial role in the HDX mechanism [7][8][9][10]19]. Beauchamp and coworkers [9] suggested that lower basicity reagents, such as D 2 O and CH 3 OD, proceed via a "relay" mechanism [20] for protonated peptides, while the higher basicity ND 3 reagent gives rise to an "onium" mechanism [21].…”

mentioning

confidence: 99%

Observation of zwitterion formation in the gas-phase H/D-exchange with CH₃OD: Solution-phase structures in the gas phase

Polfer

Dunbar

2007

J. Am. Soc. Mass Spectrom.

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Infrared spectroscopy of gas-phase singly deuterated [Trp ϩ K] ϩ (formed by H/D exchange with CH 3 OD) shows that some (ϳ20%) kinetically stable zwitterionic (ZW) conformer is formed, based on the diagnostic antisymmetric CO stretch of the deprotonated carboxylate moiety, as (CO 2 Ϫ ), at 1680 cm Ϫ1 . A majority of the deuterated [Trp ϩ K] ϩ is found to be in the charge solvation (CS) conformation, with deuterium exchange occurring on both the acid and amino groups, which is consistent with H/D scrambling. Interestingly, H/D exchange with the more basic ND 3 reagent did not result in the stabilization of a kinetically stable zwitterion, although it is not clear yet what causes this observation. The result for CH 3 OD shows that H/D exchange can in fact alter the structure of the analyte and, hence, care needs to be taken when interpreting gas-phase H/D exchange studies. Moreover, this result shows the possibility of forming solution-phase structures that are thermodynamically disfavored in the gas phase, thus opening a new area of study. (HDX) is one of the most popular techniques for the structural elucidation of biomolecules in mass spectrometry and has been widely implemented for both solution [1][2][3][4] and gas phase studies [5][6][7][8][9][10][11][12][13][14][15][16][17][18]. In solution, the extent of HDX can be directly related to the solvent accessibility of amino acid residues in proteins. However, in the gas phase there are many structural parameters apart from the surface availability that affect the HDX rates, as illustrated in a recent HDX study on ion-mobilityselected charge states of bovine ubiquitin [17]. Systematic studies on small peptide systems showed that the difference in proton affinity of the biomolecules and deuterated donor reagent plays a crucial role in the HDX mechanism [7][8][9][10]19]. Beauchamp and coworkers [9] suggested that lower basicity reagents, such as D 2 O and CH 3 OD, proceed via a "relay" mechanism [20] for protonated peptides, while the higher basicity ND 3 reagent gives rise to an "onium" mechanism [21]. In the case of amino acids cationized by an alkali metal ion rather than a proton, polar deuterating ligands such as D 2 O can exchange via a similar relay mechanism involving charge solvation-zwitterion (CS-ZW) isomerization [18]. Modeling of observed HDX processes and quantum chemical calculations of the potential surfaces have made a strong circumstantial case that ZW structures are traversed in many cases during HDX with basic partners like D 2 O, CH 3 OD, and ND 3 [14,16,18]. Nevertheless, computations also generally indicate that the bare ZW is sufficiently disfavored energetically that its equilibrium presence in the M ϩ /amino acid would be negligible [22,23].Here, we show unambiguous spectroscopic evidence that bare ZW can in fact be kinetically trapped as a result of the HDX of [Trp ϩ K] ϩ with CH 3 OD. Infrared multiple-photon dissociation (IR-MPD) spectroscopy of metal-tagged amino acids and peptides has already been shown to be a powerful probe for CS ...

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Ion-molecule reactions as probes of gas-phase structures of peptides and proteins

Cited by 237 publications

References 105 publications

Temperature-dependent H/D exchange of compact and elongated cytochrome c ions in the gas phase

Temperature-dependent H/D exchange of compact and elongated cytochrome c ions in the gas phase

Gas-Phase Structure of Protonated Histidine and Histidine Methyl Ester: Combined Experimental Mass Spectrometry and Theoretical ab Initio Study

Observation of zwitterion formation in the gas-phase H/D-exchange with CH₃OD: Solution-phase structures in the gas phase

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Ion-molecule reactions as probes of gas-phase structures of peptides and proteins

Cited by 237 publications

References 105 publications

Temperature-dependent H/D exchange of compact and elongated cytochrome c ions in the gas phase

Temperature-dependent H/D exchange of compact and elongated cytochrome c ions in the gas phase

Gas-Phase Structure of Protonated Histidine and Histidine Methyl Ester: Combined Experimental Mass Spectrometry and Theoretical ab Initio Study

Observation of zwitterion formation in the gas-phase H/D-exchange with CH3OD: Solution-phase structures in the gas phase

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Observation of zwitterion formation in the gas-phase H/D-exchange with CH₃OD: Solution-phase structures in the gas phase