Hydrogen exchange mass spectrometry resolution

Gas-Phase Fragmentation of Peptides to Increase the Spatial Resolution of the Hydrogen Exchange Mass Spectrometry Experiment... 

Kan, Z.Y., Walters, B.T., Mayne, L., Englemder, S.W. (2013) Protein hydrogen exchange at residue resolution by proteolytic fragmentation mass spectrometry emeilysis. Proc Natl Acad Sci USA, 110 (41), 16438-16443. 

Fajer, P.G., Bou-Assaf, G.M., Marshall, A.G. (2012) Improved sequence resolution by global analysis of overlapped peptides in hydrogen/deuterium exchange mass spectrometry. J Am Soc Mass Spectrom, 23 (7), 1202-1208. 

Z. Y. Kan, B. T. Walters, L. Mayne and S. W. Englander. (2013) Protein Hydrogen Exchange at Residue Resolution by Proteolytic Fragmentation Mass Spectrometry Analysis, Proceedings of the National Academy of Sciences USA, 110 (41), 16438-16443. 

Nazabal, A., Maddelein, M. L., Bonneu, M., Saupe, S. J., and Schmitter, J. M. (2005). Probing the structure of the infectious amyloid form of the prion-forming domain of HET-s using high resolution hydrogen/deuterium exchange monitored by mass spectrometry./ Biol. Chem. 280, 13220-13228. 

Dramatic advances in mass spectrometry and improvements in the various steps within the experimental hydrogen exchange procedures have resulted in the development of automated systems for high-throughput, high-resolution H/D exchange analysis [6, 8, 40-44]. 

Hydrogen-deuterium exchange experiments have been used extensively to study both structural parameters and dynamic and mechanistic aspects. They are utilized in conjunction with both NMR and IR studies. Mass spectrometry, with its high sensitivity and resolution, is ideally suited for isotopic exchange studies. 

Mass spectrometry represents a complementary approach to NMR, providing faster analysis with high sequence coverage at lower protein amounts, although usually with reduced sequence resolution. MS enables detection at subpicomole sensitivity for hydrogen exchange measurements, which for many proteins is close to physiological concentration. 

Rand, K.D., Zehl, M., Jensen, O.N., Jorgensen, T.J.D. (2009) Protein hydrogen exchange measured at single-residue resolution by electron transfer dissociation mass spectrometry. Analytical Chemistry, 81 (14), 5577-5584. 

Cravello, L., Lascoux, D., Forest, E. (2003) Use of different proteases working in acidic conditions to improve sequence coverage tmd resolution in hydrogen/deuterium exchange of large proteins. Rapid Communications in Mass Spectrometry, 17 (21), 2387-2393. 

Zhang, H.M., Kazazic, S., Schaub, T.M., et al. (2008) Enhanced digestion efficiency, peptide ionization efficiency, and sequence resolution for protein hydrogen/deuterium exchange monitored by Fourier tians-form ion cyclotron resonance mass spectrometry. Analytical Chemistry, 80 (23), 9034-9041. 

Hu, W.B., Walters, B.T., Kan, Z.Y., et al. (2013) Stepwise protein folding at near amino acid resolution by hydrogen exchange and mass spectrometry. Proceedings of the Natiorml Academy of Sciences of the United States of America, 110 (19), 7684-7689. 

Landgraf, R.R., Chalmers, M.J., Griffin, P.R. (2012) Automated hydrogen/deuterium exchange electron transfer dissociation high resolution mass spectrometry measured at single-amide resolution. J Am Soc Mass Spectrom, 23 (2), 301-309. 

Mass spectrometry offers several distinct advantages, snch as sensitivity, protein stability, and extended molecular mass, and also provides information complementary to NMR. The solubihty and pnrity of a protein arc of less concern. Furthermore, exchange rates of the most rapidly exchanging amide hydrogens can be determined. Therefore, mass spectrometry can reveal stmctnral details on transient or folding intermediates. These species may not be accessible by other conventional techniques mentioned above (e.g., NMR, CD, llnorescence) because they provide information that represents an average of entire protein ensembles. The NMR approach, on the other hand, is snperior with respect to resolution also the precious protein sample is not destroyed. 

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