6kx5
From Proteopedia
(Difference between revisions)
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<StructureSection load='6kx5' size='340' side='right'caption='[[6kx5]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='6kx5' size='340' side='right'caption='[[6kx5]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6kx5]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KX5 OCA]. For a <b>guided tour on the structure components</b> use [http:// | + | <table><tr><td colspan='2'>[[6kx5]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KX5 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6KX5 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DYR:2-carbazol-9-yl-N-(2-chloranyl-6-cyano-phenyl)ethanamide'>DYR</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DYR:2-carbazol-9-yl-N-(2-chloranyl-6-cyano-phenyl)ethanamide'>DYR</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http:// | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cry1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> |
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6kx5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kx5 OCA], [http://pdbe.org/6kx5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kx5 RCSB], [http://www.ebi.ac.uk/pdbsum/6kx5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kx5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://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> | [[http://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 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<ref>PMID:32231341</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6kx5" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Lk3 transgenic mice]] | ||
[[Category: Aikawa, Y]] | [[Category: Aikawa, Y]] | ||
[[Category: Hirota, T]] | [[Category: Hirota, T]] | ||
Revision as of 07:11, 15 April 2020
Crystal structure of mouse Cryptochrome 1 in complex with KL044 compound
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