5x18

Crystal structure of Casein kinase I homolog 1

spinqualitylabelsall models 5x18, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5x18 is a 2 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.8Å Ligands: GOL, MLA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KC11_YEAST Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Publication Abstract from PubMed Temperature compensation is a striking feature of the circadian clock. Here we investigate biochemical mechanisms underlying temperature-compensated, CKIdelta-dependent multi-site phosphorylation in mammals. We identify two mechanisms for temperature-insensitive phosphorylation at higher temperature: lower substrate affinity to CKIdelta-ATP complex and higher product affinity to CKIdelta-ADP complex. Inhibitor screening of ADP-dependent phosphatase activity of CKIdelta identified aurintricarboxylic acid (ATA) as a temperature-sensitive kinase activator. Docking simulation of ATA and mutagenesis experiment revealed K224D/K224E mutations in CKIdelta that impaired product binding and temperature-compensated primed phosphorylation. Importantly, K224D mutation shortens behavioral circadian rhythms and changes the temperature dependency of SCN's circadian period. Interestingly, temperature-compensated phosphorylation was evolutionary conserved in yeast. Molecular dynamics simulation and X-ray crystallography demonstrate that an evolutionally conserved CKI-specific domain around K224 can provide a structural basis for temperature-sensitive substrate and product binding. Surprisingly, this domain can confer temperature compensation on a temperature-sensitive TTBK1. These findings suggest the temperature-sensitive substrate- and product-binding mechanisms underlie temperature compensation. Temperature-Sensitive Substrate and Product Binding Underlie Temperature-Compensated Phosphorylation in the Clock.,Shinohara Y, Koyama YM, Ukai-Tadenuma M, Hirokawa T, Kikuchi M, Yamada RG, Ukai H, Fujishima H, Umehara T, Tainaka K, Ueda HR Mol Cell. 2017 Sep 7;67(5):783-798.e20. doi: 10.1016/j.molcel.2017.08.009. PMID:28886336 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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