The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Structures of P-glycoprotein reveal its conformational flexibility and an epitope on the nucleotide-binding domain
Open accessAbstract
P-glycoprotein (P-gp) is one of the best-known mediators of drug efflux-based multidrug resistance in many cancers. This validated therapeutic target is a prototypic, plasma membrane resident ATP-Binding Cassette transporter that pumps xenobiotic compounds out of cells. The large, polyspecific drug-binding pocket of P-gp recognizes a variety of structurally unrelated compounds. The transport of these drugs across the membrane is coincident with changes in the size and shape of this pocket during the course of the transport cycle. Here, we present the crystal structures of three inward-facing conformations of mouse P-gp derived from two different crystal forms. One structure has a nanobody bound to the C-terminal side of the first nucleotide-binding domain. This nanobody strongly inhibits the ATP hydrolysis activity of mouse P-gp by hindering the formation of a dimeric complex between the ATP-binding domains, which is essential for nucleotide hydrolysis. Together, these inward-facing conformational snapshots of P-gp demonstrate a range of flexibility exhibited by this transporter, which is likely an essential feature for the binding and transport of large, diverse substrates. The nanobody-bound structure also reveals a unique epitope on P-gp.
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Cites
Features and development of Coot
Emsley, P., Lohkamp, B., Scott, W. G., & Cowtan, K. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910007493 · Cited by 29,915
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
MolProbity : all-atom structure validation for macromolecular crystallography
Chen, V. B., Arendall, W. B., Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., Murray, L. W., Richardson, J. S., & Richardson, D. C. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909042073 · Cited by 14,115
Overview of the CCP 4 suite and current developments
Winn, M. D., Ballard, C. C., Cowtan, K. D., Dodson, E. J., Emsley, P., Evans, P. R., Keegan, R. M., Krissinel, E. B., Leslie, A. G. W., McCoy, A., et al. (2011) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444910045749 · Cited by 12,353
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. (2012) · International Tables for Crystallography · doi:10.1107/97809553602060000865 · Cited by 7,334
SWISS-MODEL: an automated protein homology-modeling server
Schwede, T. (2003) · Nucleic Acids Research · doi:10.1093/nar/gkg520 · Cited by 5,606
Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding
Aller, S. G., Yu, J., Ward, A., Weng, Y., Chittaboina, S., Zhuo, R., Harrell, P. M., Trinh, Y. T., Zhang, Q., Urbatsch, I. L., et al. (2009) · Science · doi:10.1126/science.1168750 · Cited by 1,929
Self-citationMammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview
Schinkel, A. H., & Jonker, J. W. (2003) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00169-2 · Cited by 1,386
Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview
Schinkel, A. H., & Jonker, J. W. (2012) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2012.09.027 · Cited by 1,231
Flexibility in the ABC transporter MsbA: Alternating access with a twist
Ward, A., Reyes, C. L., Yu, J., Roth, C. B., & Chang, G. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0709388104 · Cited by 771
Self-citation
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Liu, F., Zhang, Z., Csanády, L., Gadsby, D. C., & Chen, J. (2017) · Cell · doi:10.1016/j.cell.2017.02.024 · Cited by 523
Mechanisms of drug resistance in colon cancer and its therapeutic strategies
Hu, T., Li, Z., Gao, C.-Y., & Cho, C. H. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i30.6876 · Cited by 381
Structural Basis of Substrate Recognition by the Multidrug Resistance Protein MRP1
Johnson, Z. L., & Chen, J. (2017) · Cell · doi:10.1016/j.cell.2017.01.041 · Cited by 375
Refined structures of mouse P‐glycoprotein
Li, J., Jaimes, K. F., & Aller, S. G. (2014) · Protein Science · doi:10.1002/pro.2387 · Cited by 344
Metadata
- Authors
- Ward, A. B., Szewczyk, P., Grimard, V., Lee, C.-W., Martinez, L., Doshi, R., Caya, A., Villaluz, M., Pardon, E., Cregger, C., Swartz, D. J., Falson, P. G., Urbatsch, I. L., Govaerts, C., Steyaert, J., & Chang, G.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2013-07-30
- Volume
- 110
- Issue
- 33
- Pages
- 13386-13391
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2150246575
- Cited by
- 256
- References
- 43
- FWCI
- 15.49
- Type
- journal article
- Language
- en
- Open access
- green
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- Ward, A. B., Szewczyk, P., Grimard, V., Lee, C.-W., Martinez, L., Doshi, R., Caya, A., Villaluz, M., Pardon, E., Cregger, C., Swartz, D. J., Falson, P. G., Urbatsch, I. L., Govaerts, C., Steyaert, J., & Chang, G. (2013). Structures of P-glycoprotein reveal its conformational flexibility and an epitope on the nucleotide-binding domain. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.1309275110
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