Articles | Volume 2, issue 2
Research article
13 Aug 2021
Research article |  | 13 Aug 2021

High-affinity tamoxifen analogues retain extensive positional disorder when bound to calmodulin

Lilia Milanesi, Clare R. Trevitt, Brian Whitehead, Andrea M. Hounslow, Salvador Tomas, Laszlo L. P. Hosszu, Christopher A. Hunter, and Jonathan P. Waltho

Related subject area

Field: Liquid-state NMR | Topic: Applications – biological macromolecules
Facilitating the structural characterisation of non-canonical amino acids in biomolecular NMR
Sarah Kuschert, Martin Stroet, Yanni Ka-Yan Chin, Anne Claire Conibear, Xinying Jia, Thomas Lee, Christian Reinhard Otto Bartling, Kristian Strømgaard, Peter Güntert, Karl Johan Rosengren, Alan Edward Mark, and Mehdi Mobli
Magn. Reson., 4, 57–72,,, 2023
Short summary
Site-selective generation of lanthanoid binding sites on proteins using 4-fluoro-2,6-dicyanopyridine
Sreelakshmi Mekkattu Tharayil, Mithun C. Mahawaththa, Akiva Feintuch, Ansis Maleckis, Sven Ullrich, Richard Morewood, Michael J. Maxwell, Thomas Huber, Christoph Nitsche, Daniella Goldfarb, and Gottfried Otting
Magn. Reson., 3, 169–182,,, 2022
Short summary
Imatinib disassembles the regulatory core of Abelson kinase by binding to its ATP site and not by binding to its myristoyl pocket
Stephan Grzesiek, Johannes Paladini, Judith Habazettl, and Rajesh Sonti
Magn. Reson., 3, 91–99,,, 2022
Short summary
Localising nuclear spins by pseudocontact shifts from a single tagging site
Henry W. Orton, Elwy H. Abdelkader, Lydia Topping, Stephen J. Butler, and Gottfried Otting
Magn. Reson., 3, 65–76,,, 2022
Short summary
Localising individual atoms of tryptophan side chains in the metallo-β-lactamase IMP-1 by pseudocontact shifts from paramagnetic lanthanoid tags at multiple sites
Henry W. Orton, Iresha D. Herath, Ansis Maleckis, Shereen Jabar, Monika Szabo, Bim Graham, Colum Breen, Lydia Topping, Stephen J. Butler, and Gottfried Otting
Magn. Reson., 3, 1–13,,, 2022
Short summary

Cited articles

Barbato, G., Ikura, M., Kay, L. E., Pastor, R. W., and Bax, A.: Backbone dynamics of calmodulin studied by N-15 relaxation using inverse detected 2-dimensional NMR-spectroscopy – the central helix is flexible, Biochemistry, 31, 5269–5278,, 1992. 
Brown, S. C., Weber, P. L., and Mueller, L.: Toward complete H-1-NMR spectra in proteins. J. Magn. Reson., 77, 166–169,, 1988. 
Brünger, A. T.: X-PLOR. Version 3.1: A system for X-ray crystallography and NMR, Yale University Press, New Haven, CT, USA,​​​​​​​ 1992. 
Byer, S. J., Eckert, J. M., Brossier, N. M., Clodfelder-Miller, B. J., Turk, A. N., Carroll, A. J., Kappes, J. C., Zinn, K. R., Prasain, J. K., and Carroll, S. L.: Tamoxifen inhibits malignant peripheral nerve sheath tumor growth in an estrogen receptor-independent manner, Neuro-Oncology, 13, 28–41,, 2011. 
Carroll, M. J., Gromova, A. V., Miller, K. R., Tang, H., Wang, X. S., Tripathy, A., Singleton, S. F., Collins, E. J., and Lee, A. L.: Direct detection of structurally resolved dynamics in a multiconformation receptor-ligand complex, J. Am. Chem. Soc., 133, 6422–6428,, 2011. 
Short summary
The overall aim of the study is to provide a basis from which to improve the ability of tamoxifen family drugs to reduce the activity of a secondary target protein, calmodulin, during tumour development. The main conclusion is that the binding of a tamoxifen analogue is quite unlike that of other anti-calmodulin compounds in that two drug molecules bring the two domains of calmodulin into close proximity, but they are not fixed in orientation relative to the protein.