The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Probing Protein Ligand Interactions by Automated Hydrogen/Deuterium Exchange Mass Spectrometry
Abstract
Amide hydrogen/deuterium exchange is a powerful biophysical technique for probing changes in protein dynamics induced by ligand interaction. The inherent low throughput of the technology has limited its impact on drug screening and lead optimization. Automation increases the throughput of H/D exchange to make it compatible with drug discovery efforts. Here we describe the first fully automated H/D exchange system that provides highly reproducible H/D exchange kinetics from 130 ms to 24 h. Throughput is maximized by parallel sample processing, and the system can run H/D exchange assays in triplicate without user intervention. We demonstrate the utility of this system to differentiate structural perturbations in the ligand-binding domain (LBD) of the nuclear receptor PPARgamma induced upon binding a full agonist and a partial agonist. PPARgamma is the target of glitazones, drugs used for treatment of insulin resistance associated with type II diabetes. Recently it has been shown that partial agonists of PPARgamma have insulin sensitization properties while lacking several adverse effects associated with full agonist drugs. To further examine the mechanism of partial agonist activation of PPARgamma, we extended our studies to the analysis of ligand interactions with the heterodimeric complex of PPARgamma/RXRalpha LBDs. To facilitate analysis of H/D exchange of large protein complexes, we performed the experiment with a 14.5-T Fourier transform ion cyclotron resonance mass spectrometer capable of measuring mass with accuracy in the ppb range.
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Cites
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Marshall, A. G., Hendrickson, C. L., & Jackson, G. S. (1998) · Mass Spectrometry Reviews · doi:10.1002/(sici)1098-2787(1998)17:1<1::aid-mas1>3.0.co;2-k · Cited by 1,990
Self-citationLigand binding and co-activator assembly of the peroxisome proliferator-activated receptor-γ
Nolte, R. T., Wisely, G. B., Westin, S., Cobb, J. E., Lambert, M. H., Kurokawa, R., Rosenfeld, M. G., Willson, T. M., Glass, C. K., & Milburn, M. V. (1998) · Nature · doi:10.1038/25931 · Cited by 1,958
Primary structure effects on peptide group hydrogen exchange
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Hydrogen exchange and structural dynamics of proteins and nucleic acids
Englander, S. W., & Kallenbach, N. R. (1983) · Quarterly Reviews of Biophysics · doi:10.1017/s0033583500005217 · Cited by 1,356
Principles for modulation of the nuclear receptor superfamily
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Peer Reviewed: Investigating Protein Structure and Dynamics by Hydrogen Exchange MS
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“Differential HDX-MS experiments were conducted as previously described with a few modifications (Chalmers et al., 2006).”
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Solt, L. A., Kumar, N., Nuhant, P., Wang, Y., Lauer, J. L., Liu, J., Istrate, M. A., Kamenecka, T. M., Roush, W. R., Vidović, D., et al. (2011) · Nature · doi:10.1038/nature10075 · Cited by 508
Self-citationStructural Basis for the RNA-Guided Ribonuclease Activity of CRISPR-Cas13d
Zhang, C., Konermann, S., Brideau, N. J., Lotfy, P., Wu, X., Novick, S. J., Strutzenberg, T., Griffin, P. R., Hsu, P. D., & Lyumkis, D. (2018) · Cell · doi:10.1016/j.cell.2018.09.001 · Cited by 276
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Watson, E. R., Novick, S., Matyskiela, M. E., Chamberlain, P. P., H. de la Peña, A., Zhu, J., Tran, E., Griffin, P. R., Wertz, I. E., & Lander, G. C. (2022) · Science · doi:10.1126/science.add7574 · Cited by 208
Self-citationAn alternate binding site for PPARγ ligands
Hughes, T. S., Giri, P. K., de Vera, I. M. S., Marciano, D. P., Kuruvilla, D. S., Shin, Y., Blayo, A.-L., Kamenecka, T. M., Burris, T. P., Griffin, P. R., et al. (2014) · Nature Communications · doi:10.1038/ncomms4571 · Cited by 198
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Metadata
- Authors
- Chalmers, M. J., Busby, S. A., Pascal, B. D., He, Y., Hendrickson, C. L., Marshall, A. G., & Griffin, P. R.
- Venue
- Analytical Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2006-01-13
- Volume
- 78
- Issue
- 4
- Pages
- 1005-1014
- ISSN
- 0003-2700 (ISSN-L)
- 1520-6882
- OpenAlex
- W2023115763
- Cited by
- 301
- References
- 28
- FWCI
- 6.95
- Type
- journal article
- Language
- en
- Open access
- closed
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