View source for 7d19


==Crystal structure of mouse Cryptochrome 1 in complex with compound TH129==
<StructureSection load='7d19' size='340' side='right'caption='[[7d19]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7d19]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7D19 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D19 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.35&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOC:N-[2-(2,4-dimethylphenyl)-4,6-dihydrothieno[3,4-c]pyrazol-3-yl]-4-(phenylcarbonyl)benzamide'>GOC</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7d19 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d19 OCA], [https://pdbe.org/7d19 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d19 RCSB], [https://www.ebi.ac.uk/pdbsum/7d19 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d19 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CRY1_MOUSE 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.<ref>PMID:10428031</ref> <ref>PMID:16628007</ref> <ref>PMID:16478995</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
CRY1 and CRY2 proteins are highly conserved components of the circadian clock that controls daily physiological rhythms. Disruption of CRY functions are related to many diseases, including circadian sleep phase disorder. Development of isoform-selective and spatiotemporally controllable tools will facilitate the understanding of shared and distinct functions of CRY1 and CRY2. Here, we developed CRY1-selective compounds that enable light-dependent manipulation of the circadian clock. From phenotypic chemical screening in human cells, we identified benzophenone derivatives that lengthened the circadian period. These compounds selectively interacted with the CRY1 photolyase homology region, resulting in activation of CRY1 but not CRY2. The benzophenone moiety rearranged a CRY1 region called the "lid loop" located outside of the compound-binding pocket and formed a unique interaction with Phe409 in the lid loop. Manipulation of this key interaction was achieved by rationally designed replacement of the benzophenone with a switchable azobenzene moiety whose cis-trans isomerization can be controlled by light. The metastable cis form exhibited sufficiently high half-life in aqueous solutions and structurally mimicked the benzophenone unit, enabling reversible period regulation over days by cellular irradiation with visible light. This study revealed an unprecedented role of the lid loop in CRY-compound interaction and paves the way for spatiotemporal regulation of CRY1 activity by photopharmacology for molecular understanding of CRY1-dependent functions in health and disease.

Photopharmacological Manipulation of Mammalian CRY1 for Regulation of the Circadian Clock.,Kolarski D, Miller S, Oshima T, Nagai Y, Aoki Y, Kobauri P, Srivastava A, Sugiyama A, Amaike K, Sato A, Tama F, Szymanski W, Feringa BL, Itami K, Hirota T J Am Chem Soc. 2021 Jan 19. doi: 10.1021/jacs.0c12280. PMID:33464888<ref>PMID:33464888</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7d19" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cryptochrome 3D structures|Cryptochrome 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Hirota T]]
[[Category: Miller SA]]