6LUE
Crystal structure of mouse Cryptochrome 1 in complex with compound KL201
Summary for 6LUE
| Entry DOI | 10.2210/pdb6lue/pdb |
| Descriptor | Cryptochrome-1, 2-bromanyl-N-(5,6,7,8-tetrahydro-[1]benzothiolo[2,3-d]pyrimidin-4-yl)benzamide (3 entities in total) |
| Functional Keywords | cryptochrome, cry, circadian clock, kl201, circadian clock protein |
| Biological source | Mus musculus (Mouse) |
| Total number of polymer chains | 2 |
| Total formula weight | 115520.03 |
| Authors | Miller, S.,Aikawa, Y.,Hirota, T. (deposition date: 2020-01-27, release date: 2020-06-10, Last modification date: 2023-11-29) |
| Primary citation | Miller, S.,Aikawa, Y.,Sugiyama, A.,Nagai, Y.,Hara, A.,Oshima, T.,Amaike, K.,Kay, S.A.,Itami, K.,Hirota, T. An Isoform-Selective Modulator of Cryptochrome 1 Regulates Circadian Rhythms in Mammals. Cell Chem Biol, 27:1192-1198.e5, 2020 Cited by PubMed Abstract: Cryptochrome 1 (CRY1) and CRY2 are core regulators of the circadian clock, and the development of isoform-selective modulators is important for the elucidation of their redundant and distinct functions. Here, we report the identification and functional characterization of a small-molecule modulator of the mammalian circadian clock that selectively controls CRY1. Cell-based circadian chemical screening identified a thienopyrimidine derivative KL201 that lengthened the period of circadian rhythms in cells and tissues. Functional assays revealed stabilization of CRY1 but not CRY2 by KL201. A structure-activity relationship study of KL201 derivatives in combination with X-ray crystallography of the CRY1-KL201 complex uncovered critical sites and interactions required for CRY1 regulation. KL201 bound to CRY1 in overlap with FBXL3, a subunit of ubiquitin ligase complex, and the effect of KL201 was blunted by knockdown of FBXL3. KL201 will facilitate isoform-selective regulation of CRY1 to accelerate chronobiology research and therapeutics against clock-related diseases. PubMed: 32502390DOI: 10.1016/j.chembiol.2020.05.008 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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