The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Hidden alternative structures of proline isomerase essential for catalysis
Open accessAbstract
A long-standing challenge is to understand at the atomic level how protein dynamics contribute to enzyme catalysis. X-ray crystallography can provide snapshots of conformational substates sampled during enzymatic reactions, while NMR relaxation methods reveal the rates of interconversion between substates and the corresponding relative populations. However, these current methods cannot simultaneously reveal the detailed atomic structures of the rare states and rationalize the finding that intrinsic motions in the free enzyme occur on a timescale similar to the catalytic turnover rate. Here we introduce dual strategies of ambient-temperature X-ray crystallographic data collection and automated electron-density sampling to structurally unravel interconverting substates of the human proline isomerase, cyclophilin A (CYPA, also known as PPIA). A conservative mutation outside the active site was designed to stabilize features of the previously hidden minor conformation. This mutation not only inverts the equilibrium between the substates, but also causes large, parallel reductions in the conformational interconversion rates and the catalytic rate. These studies introduce crystallographic approaches to define functional minor protein conformations and, in combination with NMR analysis of the enzyme dynamics in solution, show how collective motions directly contribute to the catalytic power of an enzyme.
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[20] Processing of X-ray diffraction data collected in oscillation mode
Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475
Coot : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571
PROCHECK: a program to check the stereochemical quality of protein structures
Laskowski, R. A., MacArthur, M. W., Moss, D. S., & Thornton, J. M. (1993) · Journal of Applied Crystallography · doi:10.1107/s0021889892009944 · Cited by 24,581
Phaser crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612
The PyMOL Molecular Graphics System
DeLano, W. L. (2002) · Medical Entomology and Zoology · Cited by 18,147
NMRPipe: A multidimensional spectral processing system based on UNIX pipes
Delaglio, F., Grzesiek, S., Vuister, G., Zhu, G., Pfeifer, J., & Bax, A. (1995) · Journal of Biomolecular NMR · doi:10.1007/bf00197809 · Cited by 15,965
Investigation of exchange processes by two-dimensional NMR spectroscopy
Jeener, J., Meier, B. H., Bachmann, P., & Ernst, R. R. (1979) · The Journal of Chemical Physics · doi:10.1063/1.438208 · Cited by 4,749
PHENIX : building new software for automated crystallographic structure determination
Adams, P. D., Grosse-Kunstleve, R. W., Hung, L.-W., Ioerger, T. R., McCoy, A. J., Moriarty, N. W., Read, R. J., Sacchettini, J. C., Sauter, N. K., & Terwilliger, T. C. (2002) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444902016657 · Cited by 4,361
MolProbity: all-atom contacts and structure validation for proteins and nucleic acids
Davis, I. W., Leaver-Fay, A., Chen, V. B., Block, J. N., Kapral, G. J., Wang, X., Murray, L. W., Arendall, W. B., Snoeyink, J., Richardson, J. S., et al. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm216 · Cited by 3,896
Kabsch, W. (1993) · Journal of Applied Crystallography · doi:10.1107/s0021889893005588 · Cited by 3,578
Cited by
The ensemble nature of allostery
Motlagh, H. N., Wrabl, J. O., Li, J., & Hilser, V. J. (2014) · Nature · doi:10.1038/nature13001 · Cited by 1,247
Norris, V., Krylov, S. N., Agarwal, P. K., & White, G. J. (2017) · Microbial Physiology · doi:10.1159/000464443 · Cited by 632
Accessing protein conformational ensembles using room-temperature X-ray crystallography
Fraser, J. S., van den Bedem, H., Samelson, A. J., Lang, P. T., Holton, J. M., Echols, N., & Alber, T. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1111325108 · Cited by 615
Self-citationAn introduction to NMR-based approaches for measuring protein dynamics
Kleckner, I. R., & Foster, M. P. (2011) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2010.10.012 · Cited by 561
Studying “Invisible” Excited Protein States in Slow Exchange with a Major State Conformation
Vallurupalli, P., Bouvignies, G., & Kay, L. E. (2012) · Journal of the American Chemical Society · doi:10.1021/ja3001419 · Cited by 526
Metadata
- Authors
- Fraser, J. S., Clarkson, M. W., Degnan, S. C., Erion, R., Kern, D., & Alber, T.
- Venue
- Nature
- Published
- 2009-12
- Volume
- 462
- Issue
- 7273
- Pages
- 669-673
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2160903751
- Cited by
- 506
- References
- 44
- FWCI
- 10.68
- Type
- journal article
- Language
- en
- Open access
- green
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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