Gas-Phase Ions of Human Hemoglobin A, F, and S

Kang, Yang; Douglas, D. J.

doi:10.1007/s13361-011-0138-4

Cited by 11 publications

(11 citation statements)

References 60 publications

(97 reference statements)

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“…When ions pass through low-density gas (argon) in Q2, they lose axial kinetic energy through multiple non-reactive collisions. The energy losses can be related to collision cross sections with an aerodynamic drag model [34] by [6,10,31,35],…”

Section: Collision Cross Sections and Ms/msmentioning

confidence: 99%

“…Fragment ions are then mass analyzed in Q3. To compare relative binding strengths of the complexes, the total internal energies added to ions in Q2, ΔE int , are determined with a collision model [10,14,36], which corrects for losses of kinetic energy as the precursor ions move through the cell and for the different numbers of collisions of ions with different collision cross sections. Values of ΔE int are calculated from…”

Section: Collision Cross Sections and Ms/msmentioning

confidence: 99%

“…For H/Dx experiments, the chamber was maintained at 4 mTorr of N 2 , then filled with 6 mTorr of D 2 O vapor controlled with a needle valve (SS-SS4-Al; Swagelok, Solon, OH, USA), to a total pressure of 10 mTorr. Ions are confined axially in Q1 by adding timed DC stopping potentials to the entrance and exit lenses for up to 15 s [10]. Following this, the exit lens voltage is lowered and ions drain through a stack of lens for mass analysis with a reflectron TOF.…”

Section: Collision Cross Sections and Ms/msmentioning

confidence: 99%

“…Thus, the binding in gas-phase noncovalent complexes will not necessarily parallel solution binding. Nevertheless, some previous studies have shown that gaseous protein ions preserve, at least partially, solution-phase binding characteristics [8][9][10][11][12][13][14]. If conditions can be found where gas-phase binding is related to solution-phase binding, mass spectrometry may be more widely applied to systematically determine the relative binding strengths of a variety of molecules with a target protein, with the advantages over other methods of speed, sensitivity, and specificity.…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we have used collision cross section measurements that provide information on an ion's "size" averaged over all orientations [6,10,14], and solution-and gas-phase hydrogen/deuterium exchange (H/Dx) coupled with MS, to probe the conformations of a protein and the protein binding smallmolecule inhibitors. Tandem mass spectrometry (MS/MS) has also been used to study the relative gas-phase binding strengths of ligand-bound protein ions [10,14,15].…”

Section: Introductionmentioning

confidence: 99%

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Solution and Gas-Phase H/D Exchange of Protein–Small-Molecule Complexes: Cex and Its Inhibitors

Kang

Terrier

Ding

et al. 2011

J. Am. Soc. Mass Spectrom.

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The properties of noncovalent complexes of the enzyme exo-1,4-β-D-glycanase ("Cex") with three aza-sugar inhibitors, deoxynojirimycin (X 2 DNJ), isofagomine lactam (X 2 IL), and isofagomine (X 2 IF), have been studied with solution and gas-phase hydrogen deuterium exchange (H/Dx) and measurements of collision cross sections of gas-phase ions. In solution, complexes have lower H/Dx levels than free Cex because binding the inhibitors blocks some sites from H/Dx and reduces fluctuations of the protein. In mass spectra of complexes, abundant Cex ions are seen, which mostly are formed by dissociation of complexes in the ion sampling interface. Both complex ions and Cex ions formed from a solution containing complexes have lower cross sections than Cex ions from a solution of Cex alone. This suggests the Cex ions formed by dissociation "remember" their solution conformations. For a given charge, ions of the complexes have greater gas-phase H/Dx levels than ions of Cex. Unlike cross sections, H/Dx levels of the complexes do not correlate with the relative gas-phase binding strengths measured by MS/MS. Cex ions from solutions with or without inhibitors, which have different cross sections, show the same H/Dx level after 15 s, indicating the ions may fold or unfold on the seconds time scale of the H/Dx experiment. Thus, cross sections show that complexes have more compact conformations than free protein ions on the time scale of ca. 1 ms. The gas-phase H/Dx measurements show that at least some complexes retain different conformations from the Cex ions on a time scale of seconds.

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Section: Collision Cross Sections and Ms/msmentioning

confidence: 99%

Section: Collision Cross Sections and Ms/msmentioning

confidence: 99%

Section: Collision Cross Sections and Ms/msmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Solution and Gas-Phase H/D Exchange of Protein–Small-Molecule Complexes: Cex and Its Inhibitors

Kang

Terrier

Ding

et al. 2011

J. Am. Soc. Mass Spectrom.

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Changes in protein structure monitored by use of gas‐phase hydrogen/deuterium exchange

et al. 2015

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The study of protein conformation by solution‐phase hydrogen/deuterium exchange (HDX) coupled to MS is well documented. This involves monitoring the exchange of backbone amide protons with deuterium and provides details concerning the protein's tertiary structure. However, undesired back‐exchange during post‐HDX analyses can be difficult to control. Here, gas‐phase HDX‐MS, during which labile hydrogens on amino acid side chains are exchanged in sub‐millisecond time scales, has been employed to probe changes within protein structures. Addition of the solvent 2,2,2‐trifluoroethanol to a protein in solution can affect the structure of the protein, resulting in an increase in secondary and/or tertiary structure which is detected using circular dichroism. Using a Synapt G2‐S ESI‐mass spectrometer modified to allow deuterated ammonia into the transfer ion guide (situated between the ion mobility cell and the TOF analyser), gas‐phase HDX‐MS is shown to reflect minor structural changes experienced by the proteins β‐lactoglobulin and ubiquitin, as observed by the reduction in the level of deuterium incorporation. Additionally, the use of gas‐phase HDX‐MS to distinguish between co‐populated proteins conformers within a solution is demonstrated with the disordered protein calmodulin; the gas‐phase HDX‐MS results correspond directly with complementary data obtained by use of ion mobility spectrometry‐MS.

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Performance and geometry optimization of the ceramic‐based rectilinear ion traps

Wang

Ding

2012

Rapid Comm Mass Spectrometry

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Gas-Phase Ions of Human Hemoglobin A, F, and S

Cited by 11 publications

References 60 publications

Solution and Gas-Phase H/D Exchange of Protein–Small-Molecule Complexes: Cex and Its Inhibitors

Solution and Gas-Phase H/D Exchange of Protein–Small-Molecule Complexes: Cex and Its Inhibitors

Changes in protein structure monitored by use of gas‐phase hydrogen/deuterium exchange

Performance and geometry optimization of the ceramic‐based rectilinear ion traps

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