6kx7 | pdb_00006kx7

Crystal structure of mouse Cryptochrome 1 in complex with TH301 compound

spinqualitylabelsall models 6kx7, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6kx7 is a 1 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: DYX Gene: Cry1 (LK3 transgenic mice) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [CRY1_MOUSE] Blue light-dependent regulator of the circadian feedback loop. Inhibits CLOCK|NPAS2-ARNTL E box-mediated transcription. Acts, in conjunction with CRY2, in maintaining period length and circadian rhythmicity. Has no photolyase activity. Capable of translocating circadian clock core proteins such as PER proteins to the nucleus. May inhibit CLOCK|NPAS2-ARNTL transcriptional activity through stabilizing the unphosphorylated form of ARNTL. Publication Abstract from PubMed CRY1 and CRY2 are essential components of the circadian clock controlling daily physiological rhythms. Accumulating evidences indicate distinct roles of these highly homologous proteins, in addition to redundant functions. Therefore, the development of isoform-selective compounds represents an effective approach towards understanding the similarities and differences of CRY1 and CRY2 by controlling each isoform individually. We conducted phenotypic screenings of circadian clock modulators, and identified KL101 and TH301 that selectively stabilize CRY1 and CRY2, respectively. Crystal structures of CRY-compound complexes revealed conservation of compound-binding sites between CRY1 and CRY2. We further discovered a unique mechanism underlying compound selectivity in which the disordered C-terminal region outside the pocket was required for the differential effects of KL101 and TH301 against CRY isoforms. By using these compounds, we found a new role of CRY1 and CRY2 as enhancers of brown adipocyte differentiation, providing the basis of CRY-mediated regulation of energy expenditure. Isoform-selective regulation of mammalian cryptochromes.,Miller S, Son YL, Aikawa Y, Makino E, Nagai Y, Srivastava A, Oshima T, Sugiyama A, Hara A, Abe K, Hirata K, Oishi S, Hagihara S, Sato A, Tama F, Itami K, Kay SA, Hatori M, Hirota T Nat Chem Biol. 2020 Mar 30. pii: 10.1038/s41589-020-0505-1. doi:, 10.1038/s41589-020-0505-1. PMID:32231341 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Cryptochrome 3D structures

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