Articles | Volume 2, issue 2
https://doi.org/10.5194/mr-2-629-2021
© Author(s) 2021. This work is distributed under
the Creative Commons Attribution 4.0 License.
the Creative Commons Attribution 4.0 License.
Special issue:
https://doi.org/10.5194/mr-2-629-2021
© Author(s) 2021. This work is distributed under
the Creative Commons Attribution 4.0 License.
the Creative Commons Attribution 4.0 License.
High-affinity tamoxifen analogues retain extensive positional disorder when bound to calmodulin
Lilia Milanesi
Department of Molecular Biology and Biotechnology, University of
Sheffield, Sheffield S10 2TN, UK
Department of Biological Sciences, School of Science, Birkbeck
University of London, London WC1E 7HX, UK
Clare R. Trevitt
Department of Molecular Biology and Biotechnology, University of
Sheffield, Sheffield S10 2TN, UK
Brian Whitehead
Department of Molecular Biology and Biotechnology, University of
Sheffield, Sheffield S10 2TN, UK
Andrea M. Hounslow
Department of Molecular Biology and Biotechnology, University of
Sheffield, Sheffield S10 2TN, UK
Salvador Tomas
Department of Biological Sciences, School of Science, Birkbeck
University of London, London WC1E 7HX, UK
Departament de Química, Universitat de les Illes Balears, Cra. de Valldemossa, km 7.5. 07122 Palma de Mallorca, Spain
Laszlo L. P. Hosszu
Department of Molecular Biology and Biotechnology, University of
Sheffield, Sheffield S10 2TN, UK
Medical Research Council Prion Unit, University College of London
Institute of Neurology, Queen Square, London WCN1 3BG, UK
Christopher A. Hunter
Department of Chemistry, University of Cambridge, Lensfield Road,
Cambridge CB2 1EW, UK
Jonathan P. Waltho
CORRESPONDING AUTHOR
Department of Molecular Biology and Biotechnology, University of
Sheffield, Sheffield S10 2TN, UK
Manchester Institute of Biotechnology, University of Manchester, 131
Princess Street, Manchester M1 7DN, UK
Related subject area
Field: Liquid-state NMR | Topic: Applications – biological macromolecules
NMR side-chain assignments of the Crimean–Congo hemorrhagic fever virus glycoprotein n cytosolic domain
Facilitating the structural characterisation of non-canonical amino acids in biomolecular NMR
Site-selective generation of lanthanoid binding sites on proteins using 4-fluoro-2,6-dicyanopyridine
Imatinib disassembles the regulatory core of Abelson kinase by binding to its ATP site and not by binding to its myristoyl pocket
Localising nuclear spins by pseudocontact shifts from a single tagging site
Localising individual atoms of tryptophan side chains in the metallo-β-lactamase IMP-1 by pseudocontact shifts from paramagnetic lanthanoid tags at multiple sites
Fluorine NMR study of proline-rich sequences using fluoroprolines
Analysis of conformational exchange processes using methyl-TROSY-based Hahn echo measurements of quadruple-quantum relaxation
Anomalous amide proton chemical shifts as signatures of hydrogen bonding to aromatic sidechains
Rapid assessment of Watson–Crick to Hoogsteen exchange in unlabeled DNA duplexes using high-power SELOPE imino 1H CEST
Structural polymorphism and substrate promiscuity of a ribosome-associated molecular chaperone
Small-molecule inhibitors of the PDZ domain of Dishevelled proteins interrupt Wnt signalling
Real-time nuclear magnetic resonance spectroscopy in the study of biomolecular kinetics and dynamics
The long-standing relationship between paramagnetic NMR and iron–sulfur proteins: the mitoNEET example. An old method for new stories or the other way around?
Conformational features and ionization states of Lys side chains in a protein studied using the stereo-array isotope labeling (SAIL) method
Fragile protein folds: sequence and environmental factors affecting the equilibrium of two interconverting, stably folded protein conformations
Towards resolving the complex paramagnetic nuclear magnetic resonance (NMR) spectrum of small laccase: assignments of resonances to residue-specific nuclei
Phosphoserine for the generation of lanthanide-binding sites on proteins for paramagnetic nuclear magnetic resonance spectroscopy
Louis Brigandat, Maëlys Laux, Caroline Marteau, Laura Cole, Anja Böckmann, Lauriane Lecoq, Marie-Laure Fogeron, and Morgane Callon
Magn. Reson., 5, 95–101, https://doi.org/10.5194/mr-5-95-2024, https://doi.org/10.5194/mr-5-95-2024, 2024
Short summary
Short summary
We used NMR to sequentially assign the side-chain resonances of the cytosolic domain of glycoprotein n of the Crimean–Congo hemorrhagic fever virus. The combination of cell-free protein synthesis with high-field NMR and artificial intelligence approaches facilitated a time- and effort-efficient approach. Our results will be harnessed to study the membrane-bound form of the domain and its interactions with virulence factors, which will ultimately help to understand their role in disease.
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, https://doi.org/10.5194/mr-4-57-2023, https://doi.org/10.5194/mr-4-57-2023, 2023
Short summary
Short summary
The 20 genetically encoded amino acids provide the basis for most proteins and peptides that make up the machinery of life. This limited repertoire is vastly expanded by the introduction of non-canonical amino acids (ncAAs). Studying the structure of protein-containing ncAAs requires new computational representations that are compatible with existing modelling software. We have developed an online tool for this to aid future structural studies of this class of complex biopolymer.
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, https://doi.org/10.5194/mr-3-169-2022, https://doi.org/10.5194/mr-3-169-2022, 2022
Short summary
Short summary
Having shown that tagging a protein at a single site with different lanthanoid complexes delivers outstanding structural information at a selected site of a protein (such as active sites and ligand binding sites), we now present a simple way by which different lanthanoid complexes can be assembled on a highly solvent-exposed cysteine residue. Furthermore, the chemical assembly is selective for selenocysteine, if a selenocysteine residue can be introduced into the protein of interest.
Stephan Grzesiek, Johannes Paladini, Judith Habazettl, and Rajesh Sonti
Magn. Reson., 3, 91–99, https://doi.org/10.5194/mr-3-91-2022, https://doi.org/10.5194/mr-3-91-2022, 2022
Short summary
Short summary
We show here that binding of the anticancer drug imatinib to the ATP site of Abelson kinase and not binding to its allosteric site coincides with the opening of the kinase regulatory core at nanomolar concentrations. This has implications for the understanding of Abelson’s kinase regulation and activity during medication as well as for the design of new Abelson kinase inhibitors.
Henry W. Orton, Elwy H. Abdelkader, Lydia Topping, Stephen J. Butler, and Gottfried Otting
Magn. Reson., 3, 65–76, https://doi.org/10.5194/mr-3-65-2022, https://doi.org/10.5194/mr-3-65-2022, 2022
Short summary
Short summary
Installing a tag containing a paramagnetic metal ion on a protein can lead to large changes (pseudocontact shifts) in the resonances observed in NMR spectra. These are easily measured and contain valuable long-range structural information. The present work shows that a single tagging site furnished with different tags can be sufficient to localise atoms in proteins with high accuracy. In fact, this strategy works almost as well as the same number of tags distributed over multiple tagging 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, https://doi.org/10.5194/mr-3-1-2022, https://doi.org/10.5194/mr-3-1-2022, 2022
Short summary
Short summary
This paper explores a method for determining the solution structure of a solvent-exposed polypeptide segment (the L3 loop), which is next to the active site of the penicillin-degrading enzyme IMP-1. Tagging three different sites on the protein with paramagnetic metal ions allowed positioning of the L3 loop with atomic resolution. It was found that the method was more robust when omitting data obtained with different metal ions if obtained with the same tag at the same tagging site.
Davy Sinnaeve, Abir Ben Bouzayene, Emile Ottoy, Gert-Jan Hofman, Eva Erdmann, Bruno Linclau, Ilya Kuprov, José C. Martins, Vladimir Torbeev, and Bruno Kieffer
Magn. Reson., 2, 795–813, https://doi.org/10.5194/mr-2-795-2021, https://doi.org/10.5194/mr-2-795-2021, 2021
Short summary
Short summary
Fluorine NMR was used to study the interaction between a proline-rich peptide and a SH3 domain using 4S- and 4R-fluorinated prolines whose potential as NMR probes has not been exploited yet. We present a comprehensive study addressing several aspects to be considered when using these residues as NMR probes, including relaxation and dynamics. We show that their conformational bias may be used to modulate the kinetics of protein binding to proline-rich motifs.
Christopher A. Waudby and John Christodoulou
Magn. Reson., 2, 777–793, https://doi.org/10.5194/mr-2-777-2021, https://doi.org/10.5194/mr-2-777-2021, 2021
Short summary
Short summary
We describe a suite of experiments that exploit field-dependent relaxation measurements of four-spin transitions in methyl groups to characterise chemical exchange processes and which can be used as an alternative or complement to CPMG relaxation dispersion measurements. We show that these four-spin transitions benefit from the methyl TROSY effect and so provide a unique combination of slow intrinsic relaxation and high sensitivity to chemical exchange.
Kumaran Baskaran, Colin W. Wilburn, Jonathan R. Wedell, Leonardus M. I. Koharudin, Eldon L. Ulrich, Adam D. Schuyler, Hamid R. Eghbalnia, Angela M. Gronenborn, and Jeffrey C. Hoch
Magn. Reson., 2, 765–775, https://doi.org/10.5194/mr-2-765-2021, https://doi.org/10.5194/mr-2-765-2021, 2021
Short summary
Short summary
The Biological Magnetic Resonance Data Bank (BMRB) has been used to identify overall trends, for example, the relationship between chemical shift and backbone conformation. The BMRB archive has grown so that statistical outliers are sufficiently numerous to afford insights into unusual or unique structural features in proteins. We analyze amide proton chemical shift outliers to gain insights into the occurrence of hydrogen bonds between an amide NH and the p-pi cloud of aromatic sidechains.
Bei Liu, Atul Rangadurai, Honglue Shi, and Hashim M. Al-Hashimi
Magn. Reson., 2, 715–731, https://doi.org/10.5194/mr-2-715-2021, https://doi.org/10.5194/mr-2-715-2021, 2021
Short summary
Short summary
There is growing interest in mapping exchange dynamics between Watson–Crick and Hoogsteen conformations across different DNA contexts. However, current methods are ill-suited for measurements at a large scale because they require isotopically enriched samples. We report that Hoogsteen dynamics can be measured on unlabeled samples using 1H CEST experiments, which have higher throughput and lower cost relative to conventional methods and also provide new insights into Hoogsteen dynamics.
Chih-Ting Huang, Yei-Chen Lai, Szu-Yun Chen, Meng-Ru Ho, Yun-Wei Chiang, and Shang-Te Danny Hsu
Magn. Reson., 2, 375–386, https://doi.org/10.5194/mr-2-375-2021, https://doi.org/10.5194/mr-2-375-2021, 2021
Short summary
Short summary
Trigger factor (TF) is a conserved bacterial molecular chaperone that exists in a monomer–dimer equilibrium in solution. It binds to the ribosome as a monomer to facilitate folding of nascent polypeptide chains. We showed that dimeric TF exhibits distinct domain dynamics and conformational polymorphism and that TF contains multiple substrate binding sites that are only accessible in its monomeric form. The equilibrium of TF in different oligomeric states may serve as a regulatory mechanism.
Nestor Kamdem, Yvette Roske, Dmytro Kovalskyy, Maxim O. Platonov, Oleksii Balinskyi, Annika Kreuchwig, Jörn Saupe, Liang Fang, Anne Diehl, Peter Schmieder, Gerd Krause, Jörg Rademann, Udo Heinemann, Walter Birchmeier, and Hartmut Oschkinat
Magn. Reson., 2, 355–374, https://doi.org/10.5194/mr-2-355-2021, https://doi.org/10.5194/mr-2-355-2021, 2021
Short summary
Short summary
The Wnt signalling pathway plays a major role in prevention of cancer, whereby the protein Dishevelled connects from the transmembrane receptor Frizzled to downstream effectors via its PDZ domain. Here, cycles of chemical synthesis and structural biology are applied to develop PDZ ligands that block the Frizzled–Dishevelled interaction using NMR for screening, in ligand development, and for deriving structure–activity relationships. Cellular reporter assays demonstrate their efficacy.
György Pintér, Katharina F. Hohmann, J. Tassilo Grün, Julia Wirmer-Bartoschek, Clemens Glaubitz, Boris Fürtig, and Harald Schwalbe
Magn. Reson., 2, 291–320, https://doi.org/10.5194/mr-2-291-2021, https://doi.org/10.5194/mr-2-291-2021, 2021
Short summary
Short summary
The folding, refolding and misfolding of biomacromolecules including proteins, DNA and RNA is an important area of biophysical research to understand functional and disease states of a cell. NMR spectroscopy provides detailed insight, with both high time and atomic resolution. These experiments put stringent requirements on signal-to-noise for often irreversible folding reactions. The review describes methodological approaches and highlights key applications.
Francesca Camponeschi, Angelo Gallo, Mario Piccioli, and Lucia Banci
Magn. Reson., 2, 203–221, https://doi.org/10.5194/mr-2-203-2021, https://doi.org/10.5194/mr-2-203-2021, 2021
Short summary
Short summary
The iron–sulfur cluster binding properties of human mitoNEET have been investigated by 1D and 2D 1H paramagnetic NMR spectroscopy. The NMR spectra of both oxidized and reduced mitoNEET are significantly different from those reported previously for other [Fe2S2] proteins. Our findings revealed the unique electronic properties of mitoNEET and suggests that the specific electronic structure of the cluster possibly drives the functional properties of different [Fe2S2] proteins.
Mitsuhiro Takeda, Yohei Miyanoiri, Tsutomu Terauchi, and Masatsune Kainosho
Magn. Reson., 2, 223–237, https://doi.org/10.5194/mr-2-223-2021, https://doi.org/10.5194/mr-2-223-2021, 2021
Short summary
Short summary
Although both the hydrophobic aliphatic chain and hydrophilic ζ-amino group of the lysine side chain presumably contribute to the structures and functions of proteins, the dual nature of the lysine residue has not been fully understood yet, due to the lack of appropriate methods to acquire comprehensive information on its long consecutive methylene chain at the atomic scale. We describe herein a novel strategy to address the current situation using nuclear magnetic resonance spectroscopy.
Xingjian Xu, Igor Dikiy, Matthew R. Evans, Leandro P. Marcelino, and Kevin H. Gardner
Magn. Reson., 2, 63–76, https://doi.org/10.5194/mr-2-63-2021, https://doi.org/10.5194/mr-2-63-2021, 2021
Short summary
Short summary
While most proteins adopt one conformation, several interconvert between two or more very different structures. Knowing how sequence changes and small-molecule binding can control this behavior is essential for both understanding biology and inspiring new “molecular switches” which can control cellular pathways. This work contributes by examining these topics in the ARNT protein, showing that features of both the folded and unfolded states contribute to the interconversion process.
Rubin Dasgupta, Karthick B. S. S. Gupta, Huub J. M. de Groot, and Marcellus Ubbink
Magn. Reson., 2, 15–23, https://doi.org/10.5194/mr-2-15-2021, https://doi.org/10.5194/mr-2-15-2021, 2021
Short summary
Short summary
A method is demonstrated that can help in sequence-specific NMR signal assignment to nuclear spins near a strongly paramagnetic metal in an enzyme. A combination of paramagnetically tailored NMR experiments and second-shell mutagenesis was used to attribute previously observed chemical exchange processes in the active site of laccase to specific histidine ligands. The signals of nuclei close to the metal can be used as spies to unravel the role of motions in the catalytic process.
Sreelakshmi Mekkattu Tharayil, Mithun Chamikara Mahawaththa, Choy-Theng Loh, Ibidolapo Adekoya, and Gottfried Otting
Magn. Reson., 2, 1–13, https://doi.org/10.5194/mr-2-1-2021, https://doi.org/10.5194/mr-2-1-2021, 2021
Short summary
Short summary
A new way is presented for creating lanthanide binding sites on proteins using site-specifically introduced phosphoserine residues. The paramagnetic effects of lanthanides generate long-range effects, which contain structural information and are readily measured by NMR spectroscopy. Excellent correlations between experimentally observed and back-calculated pseudocontact shifts attest to very good immobilization of the lanthanide ions relative to the proteins.
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, https://doi.org/10.1021/bi00138a005, 1992.
Brown, S. C., Weber, P. L., and Mueller, L.: Toward complete H-1-NMR spectra
in proteins. J. Magn. Reson., 77, 166–169, https://doi.org/10.1016/0022-2364(88)90042-x,
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, https://doi.org/10.1093/neuonc/noq146, 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,
https://doi.org/10.1021/ja2005253, 2011.
Chattopadhyaya, R., Meador, W. E., Means, A. R., and Quiocho, F. A.:
Calmodulin structure refined at 1.7 Angstrom resolution, J. Mol. Biol., 228,
1177–1192, https://doi.org/10.1016/0022-2836(92)90324-D, 1992.
Chou, J. J., Li, S. P., Klee, C. B., and Bax, A.: Solution structure of
Ca2+-calmodulin reveals flexible hand-like properties of its domains, Nat.
Struct. Biol., 8, 990–997, https://doi.org/10.3410/f.1002399.26607, 2001.
Cifuentes, E., Mataraza, J. M., Yoshida, B. A., Menon, M., Sacks, D. B.,
Barrack, E. R., and Reddy, G. P. V.: Physical and functional interaction of
androgen receptor with calmodulin in prostate cancer cells, P. Natl.
Acad. Sci. USA, 101, 464–469, https://doi.org/10.1073/pnas.0307161101, 2004.
Craven, C. J., Whitehead, B., Jones, S. K. A., Thulin, E., Blackburn, G. M.,
and Waltho, J. P.: Complexes formed between calmodulin and the antagonists
J-8 and TFP in solution, Biochemistry, 35, 10287–10299,
https://doi.org/10.1021/bi9605043, 1996.
Dolan, K., Montgomery, S., Buchheit, B., DiDone, L., Wellington, M., and
Krysan, D. J.: Antifungal activity of tamoxifen: In vitro and in vivo
activities and mechanistic characterization, Antimicrob. Agents Ch., 53,
3337–3346, https://doi.org/10.1128/aac.01564-08, 2009.
Dowsett, M., Dixon, J. M., Horgan, K., Salter, J., Hills, M., and Harvey,
E.: Antiproliferative effects of idoxifene in a placebo-controlled trial in
primary human breast cancer, Clin. Cancer Res., 6, 2260–2267, 2000.
Edwards, K. J., Laughton, C. A., and Neidle, S.: A molecular modeling study
of the interactions between the antiestrogen drug tamoxifen and several
derivatives, and the calcium-binding protein calmodulin, J. Med. Chem., 35,
2753–2761, https://doi.org/10.1021/jm00093a006, 1992.
Elshorst, B., Hennig, M., Forsterling, H., Diener, A., Maurer, M., Schulte,
P., Schwalbe, H., Griesinger, C., Krebs, J., Schmid, H., Vorherr, T., and
Carafoli, E.: NMR solution structure of a complex of calmodulin with a
binding peptide of the Ca2+ pump, Biochemistry, 38, 12320–12332,
https://doi.org/10.1021/bi9908235, 1999.
Finn, B. E., Evenas, J., Drakenberg, T., Waltho, J. P., Thulin, E., and
Forsen, S.: Calcium-induced structural-changes and domain autonomy in
calmodulin, Nat. Struct. Biol., 2, 777–783, https://doi.org/10.1038/nsb0995-777, 1995.
Frederick, K. K., Marlow, M. S., Valentine, K. G., and Wand, A. J.:
Conformational entropy in molecular recognition by proteins, Nature, 448,
325–329, https://doi.org/10.1038/nature05959, 2007.
Gallo, D., Jacquot, Y., Laurent, G., and Leclercq, G.: Calmodulin, a
regulatory partner of the estrogen receptor alpha in breast cancer cells,
Mol. Cell. Endocrinol., 291, 20–26, https://doi.org/10.1016/j.mce.2008.04.011, 2008.
Gulino, A., Barrera, G., Vacca, A., Farina, A., Ferretti, C., Screpanti, I.,
Dianzani, M. U., and Frati, L.: Calmodulin antagonism and growth-inhibiting
activity of triphenylethylene antiestrogens in Mcf-7 human-breast
cancer-cells, Cancer Research, 46, 6274–6278,
1986.
Hardcastle, I. R., Rowlands, M. G., Houghton, J., Parr, I. B., Potter, G.
A., Jarman, M., Edwards, K. J., Laughton, C. A., Trent, J. O., and Neidle,
S.: Rationally designed analogs of tamoxifen with improved calmodulin
antagonism, J. Med. Chem., 38, 241–248, https://doi.org/10.1021/jm00002a005, 1995.
Hardcastle, I. R., Rowlands, M. G., Grimshaw, R. M., Houghton, J., Jarman,
M., Sharff, A., and Neidle, S.: Homologs of idoxifene: Variation of estrogen
receptor binding and calmodulin antagonism with chain length, J. Med. Chem.,
39, 999–1004, https://doi.org/10.1021/jm9505472, 1996.
Harmat, V., Bocskei, Z., Naray-Szabo, G., Bata, I., Csutor, A. S., Hermecz,
I., Aranyi, P., Szabo, B., Liliom, K., Vertessy, B., and Ovadi, J.: A new
potent calmodulin antagonist with arylalkylamine structure:
Crystallographic, spectroscopic and functional studies, J. Mol. Biol., 297,
747–755, https://doi.org/10.1006/jmbi.2000.3607, 2000.
Horvath, I., Harmat, V., Perczel, A., Palfi, V., Nyitray, L., Nagy, A.,
Hlavanda, E., Naray-Szabo, G., and Ovadi, J.: The structure of the complex
of calmodulin with KAR-2 – A novel mode of binding explains the unique
pharmacology of the drug, J. Biol. Chem., 280, 8266–8274,
https://doi.org/10.1074/jbc.m410353200, 2005.
Hughes, T. S., Chalmers, M. J., Novick, S., Kuruvilla, D. S., Ra Chang, M.,
Kamenecka, T. M., Rance, M., Johnson, B. A., Burris, T. P., Griffin, P. R.,
and Kojetin, D. J.: Ligand and receptor dynamics contribute to the mechanism
of graded PPAR gamma agonism, Structure, 20, 139–150,
https://doi.org/10.1016/j.str.2011.10.018, 2012.
Ikura, M. and Ames, J. B.: Genetic polymorphism and protein conformational
plasticity in the calmodulin superfamily: Two ways to promote
multifunctionality, P. Natl. Acad. Sci. USA, 103, 1159–1164,
https://doi.org/10.1073/pnas.0508640103, 2006.
Ikura, M., Kay, L. E., Krinks, M., and Bax, A.: Triple-resonance
multidimensional NMR-study of calmodulin complexed with the binding domain
of skeletal-muscle myosin light-chain kinase – Indication of a
conformational change in the central helix, Biochemistry, 30, 5498–5504,
https://doi.org/10.1021/bi00236a024, 1991.
Ikura, M., Clore, G. M., Gronenborn, A. M., Zhu, G., Klee, C. B., and Bax,
A.: Solution structure of a calmodulin-target peptide complex by
multidimensional NMR, Science, 256, 632–638, https://doi.org/10.1126/science.1585175,
1992.
Izumi, Y., Watanabe, H., Watanabe, N., Aoyama, A., Jinbo, Y., and Hayashi,
N.: Solution X-ray scattering reveals a novel structure of calmodulin
complexed with a binding domain peptide from the HIV-1 matrix protein p17,
Biochemistry, 47, 7158–7166, https://doi.org/10.1021/bi702416b, 2008.
Kovesi, I., Menyhard, D. K., Laberge, M., and Fidy, J.: Interaction of
antagonists with calmodulin: Insights from molecular dynamics simulations,
J. Med. Chem., 51, 3081–3093, https://doi.org/10.1021/jm701406e, 2008.
Kuboniwa, H., Tjandra, N., Grzesiek, S., Ren, H., Klee, C. B., and Bax, A.:
Solution structure of calcium-free calmodulin, Nat. Struct. Biol., 2,
768–776, https://doi.org/10.1038/nsb0995-768, 1995.
Li, L. and Sacks, D. B.: Functional interactions between calmodulin and
estrogen receptor-alpha, Cell Signal., 19, 439–443,
https://doi.org/10.1016/j.cellsig.2006.08.018, 2007.
Linse, S., Helmersson, A., and Forsen, S.: Calcium-binding to calmodulin and
its globular domains, J. Biol. Chem., 266, 8050–8054, 1991.
MacGregor, J. I. and Jordan V. C.: Basic guide to the mechanisms of
antiestrogen action, Pharmacol. Rev., 50, 151–196, 1998.
MacNeil, S., Griffin, M., Cooke, A. M., Pettett, N. J., Dawson, R. A., Owen,
R., and Blackburn, G. M.: Calmodulin antagonists of improved potency and
specificity for use in the study of calmodulin biochemistry, Biochem.
Pharmacol., 37, 1717–1723, https://doi.org/10.1016/0006-2952(88)90434-0, 1988.
Marshall, E.: Tamoxifen – 'A big deal', but a complex hand to play, Science,
280, 196–196, https://doi.org/10.1126/science.280.5361.196b, 1998.
Maximciuc, A. A., Putkey, J. A., Shamoo, Y., and MacKenzie, K. R.: Complex
of calmodulin with a ryanodine receptor target reveals a novel, flexible
binding mode, Structure, 14, 1547–1556, https://doi.org/10.1016/j.str.2006.08.011, 2006.
McConnell, H. M.: Reaction rates by Nuclear Magnetic Resonance, J. Chem.
Phys., 28, 430–431, 1958.
Meador, W. E., Means, A. R., and Quiocho, F. A.: Target enzyme recognition
by calmodulin – 2.4-Angstrom structure of a calmodulin-peptide complex,
Science, 257, 1251–1255, https://doi.org/10.1126/science.1519061, 1992.
Milanesi, L., Trevitt, C. R., Whitehead, B., Hounslow, A. M., Tomas, S., Hosszu, L. L. P., Hunter, C. A., and Waltho, J. P.: Idoxifene:Calmodulin complex structures, ORDA [data set], https://doi.org/10.15131/shef.data.15113511, 2021.
Nilges, M.: Calculation of protein structures with ambiguous distance
restraints – Automated assignment of ambiguous NOE crosspeaks and disulfide
connectivities, J. Mol. Biol., 245, 645–660,
https://doi.org/10.1006/jmbi.1994.0053, 1995.
Osawa, M., Swindells, M. B., Tanikawa, J., Tanaka, T., Mase, T., Furuya, T.,
and Ikura, M.: Solution structure of calmodulin-W-7 complex: The basis of
diversity in molecular recognition, J. Mol. Biol., 276, 165–176,
https://doi.org/10.1006/jmbi.1997.1524, 1998.
Osawa, M., Kuwamoto, S., Izumi, Y., Yap, K. L., Ikura, M., Shibanuma, T.,
Yokokura, H., Hidaka, H., and Matsushima, N.: Evidence for calmodulin
inter-domain compaction in solution induced by W-7 binding, FEBS Lett., 442,
173–177, https://doi.org/10.1016/s0014-5793(98)01637-8, 1999.
Pawar, P., Ma, L. P., Byon, C. H., Liu, H., Ahn, E. Y., Jhala, N.,
Arnoletti, J. P., McDonald, J. M., and Chen, Y. B.: Molecular mechanisms of
tamoxifen therapy for cholangiocarcinoma: Role of calmodulin, Clin. Cancer
Res., 15, 1288–1296, https://doi.org/10.1158/1078-0432.ccr-08-1150, 2009.
Powles, T. J.: Extended adjuvant tamoxifen for breast cancer–a new era?,
Lancet, 381, 782–783, https://doi.org/10.1016/s0140-6736(12)62038-8, 2013.
Prozialeck, W. C. and Weiss, B.: Inhibition of calmodulin by phenothiazines
and related drugs – Structure-Activity-Relationships, J. Pharmacol. Exp.
Ther., 222, 509–516, 1982.
Reid, D. G., Maclachlan, L. K., Gajjar, K., Voyle, M., King, R. J., and
England, P. J.: A Proton nuclear-magnetic-resonance and molecular modeling
study of calmidazolium (R24571) binding to calmodulin and skeletal-muscle
troponin-C, J. Biol. Chem., 265, 9744–9753,
https://doi.org/10.1016/S0021-9258(19)38734-4, 1990.
Samal, A. B., Ghanam, R. H., Fernandez, T. F., Monroe, E. B., and Saad, J.
S.: NMR, biophysical, and biochemical studies reveal the minimal calmodulin
binding domain of the HIV-1 matrix protein, J. Biol. Chem., 286,
33533–33543, https://doi.org/10.1074/jbc.m111.273623, 2011.
Shiau, A. K., Barstad, D., Loria, P. M., Cheng, L., Kushner, P. J., Agard,
D. A., and Greene, G. L.: The structural basis of estrogen
receptor/coactivator recognition and the antagonism of this interaction by
tamoxifen, Cell, 95, 927–937, https://doi.org/10.1016/s0092-8674(00)81717-1, 1998.
Swulius, M. T. and Waxham, M. N.: Ca calmodulin-dependent protein
kinases, Cell. Mol. Life Sci., 65, 2637–2657, https://doi.org/10.1007/s00018-008-8086-2,
2008.
Takeuchi, K., Tokunaga, Y., Imai, M., Takahashi, H., and Shimada, I.:
Dynamic multidrug recognition by multidrug transcriptional repressor LmrR,
Sci. Rep., 4, 6922, https://doi.org/10.1038/srep06922, 2014.
Trevitt, C. R., Craven, C. J., Milanesi, L., Syson, K., Mattinen, M. L.,
Perkins, J., Annila, A., Hunter, C. A., and Waltho, J. P.: Enhanced ligand
affinity for receptors in which components of the binding site are
independently mobile, Chem. Biol., 12, 89–97,
https://doi.org/10.1016/j.chembiol.2004.11.007, 2005.
Vandonselaar, M., Hickie, R. A., Quail, J. W., and Delbaere, L. T. J.:
Trifluoperazine-induced conformational change in Ca2+-calmodulin, Nat.
Struct. Biol., 1, 795–801, https://doi.org/10.1038/nsb1194-795, 1994.
Vogel, H. J., Lindahl, L., and Thulin, E.: Calcium-dependent hydrophobic
interaction chromatography of calmodulin, troponin-C and their proteolytic
fragments, FEBS Lett., 157, 241–246, https://doi.org/10.1016/0014-5793(83)80554-7, 1983.
Wishart, D. S., Bigam, C. G., Yao, J., Abildgaard, F., Dyson, H. J.,
Oldfield, E., Markley, J. L., and Sykes, B. D.: 1H, 13C and 15N
chemical-shift referencing in biomolecular NMR, J. Biomol. NMR., 6, 135–140,
https://doi.org/10.1007/bf00211777, 1995.
Yamauchi, E., Nakatsu, T., Matsubara, M., Kato, H., and Taniguchi, H.:
Crystal structure of a MARCKS peptide containing the calmodulin-binding
domain in complex with Ca2+-calmodulin, Nat. Struct. Biol., 10, 226–231,
https://doi.org/10.1038/nsb900, 2003.
Zhang, M., Tanaka, T., and Ikura, M.: Calcium-induced conformational
transition revealed by the solution structure of apo calmodulin, Nat.
Struct. Biol., 2, 758–767, https://doi.org/10.1038/nsb0995-758, 1995.
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.
The overall aim of the study is to provide a basis from which to improve the ability of...
Special issue