The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Breaking Cryo-EM Resolution Barriers to Facilitate Drug Discovery
Open accessAbstract
SUMMARY Recent advances in single-particle cryoelecton microscopy (cryo-EM) are enabling generation of numerous near-atomic-resolution structures for well-ordered protein complexes with sizes ≥ ~200 kDa. Whether cryo-EM methods are equally useful for high-resolution structural analysis of smaller, dynamic protein complexes such as those involved in cellular metabolism remains an important question. Here, we present 3.8 Å resolution cryo-EM structures of isocitrate dehydrogenase (93 kDa) and identify the nature of conformational changes induced by binding of the allosteric small-molecule inhibitor ML309. We also report 2.8-Å- and 1.8-Å-resolution structures of the cancer targets lactate dehydrogenase (145 kDa) and glutamate dehydrogenase (334 kDa), respectively. With these results, two perceived barriers in single-particle cryo-EM are overcome: our tests demonstrated crossing 2 Å resolution and obtaining maps of proteins with sizes < 100 kDa, demonstrating that cryo-EM can be used to investigate a broad spectrum of drug-target interactions and dynamic conformational states.
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PHENIX : a comprehensive Python-based system for macromolecular structure solution
Adams, P. D., Afonine, P. V., Bunkóczi, G., Chen, V. B., Davis, I. W., Echols, N., Headd, J. J., Hung, L.-W., Kapral, G. J., Grosse-Kunstleve, R. W., et al. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909052925 · Cited by 23,716
Cancer-associated IDH1 mutations produce 2-hydroxyglutarate
Dang, L., White, D. W., Gross, S., Bennett, B. D., Bittinger, M. A., Driggers, E. M., Fantin, V. R., Jang, H. G., Jin, S., Keenan, M. C., et al. (2009) · Nature · doi:10.1038/nature08617 · Cited by 4,154
Structures of the E. coli translating ribosome with SRP and its receptor and with the translocon
Jomaa, A., Boehringer, D., Leibundgut, M., & Ban, N. (2016) · Nature Communications · doi:10.1038/ncomms10471 · Cited by 115
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Phelps, J. S., Hildebrand, D. G. C., Graham, B. J., Kuan, A. T., Thomas, L. A., Nguyen, T. M., Buhmann, J., Azevedo, A. W., Sustar, A., Agrawal, S., et al. (2021) · Cell · doi:10.1016/j.cell.2020.12.013 · Cited by 265
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Guo, H., Bueler, S. A., & Rubinstein, J. L. (2017) · Science · doi:10.1126/science.aao4815 · Cited by 225
Dang, L., & Su, S.-S. M. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-061516-044732 · Cited by 204
Atomic-resolution three-dimensional hydration structures on a heterogeneously charged surface
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Main methods and tools for peptide development based on protein-protein interactions (PPIs)
Baeza, J., Bedoya, M., Cruz, P., Ojeda, P., Adasme-Carreño, F., Cerda, O., & González, W. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.151623 · Cited by 8
Cryo-EM reveals the structure and dynamics of a 723-residue malate synthase G
Ho, M.-R., Wu, Y.-M., Lu, Y.-C., Ko, T.-P., & Wu, K.-P. (2023) · Journal of Structural Biology · doi:10.1016/j.jsb.2023.107958 · Cited by 8
Metadata
- Authors
- Merk, A., Bartesaghi, A., Banerjee, S., Falconieri, V., Rao, P., Davis, M. I., Pragani, R., Boxer, M. B., Earl, L. A., Milne, J. L. S., & Subramaniam, S.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-06
- Volume
- 165
- Issue
- 7
- Pages
- 1698-1707
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2397429809
- Cited by
- 504
- References
- 3
- FWCI
- 47.47
- Type
- journal article
- Language
- en
- Open access
- bronze
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