Vitamin D Analogs Bearing C-20 Modifications Stabilize the Agonistic Conformation of Non-Responsive Vitamin D Receptor Variants
The Vitamin D receptor (VDR) plays a key role in calcium homeostasis, as well as in cell proliferation and differentiation. Among the large number of VDR ligands that have been developed, we have previously shown that BXL-62 and Gemini-72, two C-20-modified vitamin D analogs are highly potent VDR ag...
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| Format: | Article |
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MDPI AG
2022-07-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/15/8445 |
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| author | Anna Y. Belorusova Daniela Rovito Yassmine Chebaro Stefanie Doms Lieve Verlinden Annemieke Verstuyf Daniel Metzger Natacha Rochel Gilles Laverny |
| author_facet | Anna Y. Belorusova Daniela Rovito Yassmine Chebaro Stefanie Doms Lieve Verlinden Annemieke Verstuyf Daniel Metzger Natacha Rochel Gilles Laverny |
| author_sort | Anna Y. Belorusova |
| collection | DOAJ |
| description | The Vitamin D receptor (VDR) plays a key role in calcium homeostasis, as well as in cell proliferation and differentiation. Among the large number of VDR ligands that have been developed, we have previously shown that BXL-62 and Gemini-72, two C-20-modified vitamin D analogs are highly potent VDR agonists. In this study, we show that both VDR ligands restore the transcriptional activities of VDR variants unresponsive to the natural ligand and identified in patients with rickets. The elucidated mechanisms of action underlying the activities of these C-20-modified analogs emphasize the mutual adaptation of the ligand and the VDR ligand-binding pocket. |
| first_indexed | 2024-03-09T12:32:46Z |
| format | Article |
| id | doaj.art-5252e406bde940ce937811cf1cef9b09 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:32:46Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5252e406bde940ce937811cf1cef9b092023-11-30T22:28:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-07-012315844510.3390/ijms23158445Vitamin D Analogs Bearing C-20 Modifications Stabilize the Agonistic Conformation of Non-Responsive Vitamin D Receptor VariantsAnna Y. Belorusova0Daniela Rovito1Yassmine Chebaro2Stefanie Doms3Lieve Verlinden4Annemieke Verstuyf5Daniel Metzger6Natacha Rochel7Gilles Laverny8Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), F-67400 Illkirch, FranceInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), F-67400 Illkirch, FranceInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), F-67400 Illkirch, FranceClinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, 3000 Leuven, BelgiumClinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, 3000 Leuven, BelgiumClinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, 3000 Leuven, BelgiumInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), F-67400 Illkirch, FranceInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), F-67400 Illkirch, FranceInstitut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), F-67400 Illkirch, FranceThe Vitamin D receptor (VDR) plays a key role in calcium homeostasis, as well as in cell proliferation and differentiation. Among the large number of VDR ligands that have been developed, we have previously shown that BXL-62 and Gemini-72, two C-20-modified vitamin D analogs are highly potent VDR agonists. In this study, we show that both VDR ligands restore the transcriptional activities of VDR variants unresponsive to the natural ligand and identified in patients with rickets. The elucidated mechanisms of action underlying the activities of these C-20-modified analogs emphasize the mutual adaptation of the ligand and the VDR ligand-binding pocket.https://www.mdpi.com/1422-0067/23/15/8445structure function relationshipvitamin Drare diseases |
| spellingShingle | Anna Y. Belorusova Daniela Rovito Yassmine Chebaro Stefanie Doms Lieve Verlinden Annemieke Verstuyf Daniel Metzger Natacha Rochel Gilles Laverny Vitamin D Analogs Bearing C-20 Modifications Stabilize the Agonistic Conformation of Non-Responsive Vitamin D Receptor Variants International Journal of Molecular Sciences structure function relationship vitamin D rare diseases |
| title | Vitamin D Analogs Bearing C-20 Modifications Stabilize the Agonistic Conformation of Non-Responsive Vitamin D Receptor Variants |
| title_full | Vitamin D Analogs Bearing C-20 Modifications Stabilize the Agonistic Conformation of Non-Responsive Vitamin D Receptor Variants |
| title_fullStr | Vitamin D Analogs Bearing C-20 Modifications Stabilize the Agonistic Conformation of Non-Responsive Vitamin D Receptor Variants |
| title_full_unstemmed | Vitamin D Analogs Bearing C-20 Modifications Stabilize the Agonistic Conformation of Non-Responsive Vitamin D Receptor Variants |
| title_short | Vitamin D Analogs Bearing C-20 Modifications Stabilize the Agonistic Conformation of Non-Responsive Vitamin D Receptor Variants |
| title_sort | vitamin d analogs bearing c 20 modifications stabilize the agonistic conformation of non responsive vitamin d receptor variants |
| topic | structure function relationship vitamin D rare diseases |
| url | https://www.mdpi.com/1422-0067/23/15/8445 |
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