4jjr
A P21 crystal form of mammalian casein kinase 1 delta
Structural highlights
FunctionKC1D_MOUSE Essential serine/threonine-protein kinase that regulates diverse cellular growth and survival processes including Wnt signaling, DNA repair and circadian rhythms. It can phosphorylate a large number of proteins. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Phosphorylates connexin-43/GJA1, MAP1A, SNAPIN, MAPT/TAU, TOP2A, DCK, HIF1A, EIF6, p53/TP53, DVL2, DVL3, ESR1, AIB1/NCOA3, DNMT1, PKD2, YAP1, PER1 and PER2. Central component of the circadian clock. May act as a negative regulator of circadian rhythmicity by phosphorylating PER1 and PER2, leading to retain PER1 in the cytoplasm. YAP1 phosphorylation promotes its SCF(beta-TRCP) E3 ubiquitin ligase-mediated ubiquitination and subsequent degradation. DNMT1 phosphorylation reduces its DNA-binding activity. Phosphorylation of ESR1 and AIB1/NCOA3 stimulates their activity and coactivation. Phosphorylation of DVL2 and DVL3 regulates WNT3A signaling pathway that controls neurite outgrowth. EIF6 phosphorylation promotes its nuclear export. Triggers down-regulation of dopamine receptors in the forebrain. Activates DCK in vitro by phosphorylation. TOP2A phosphorylation favors DNA cleavable complex formation. May regulate the formation of the mitotic spindle apparatus in extravillous trophoblast. Modulates connexin-43/GJA1 gap junction assembly by phosphorylation. Probably involved in lymphocyte physiology. Regulates fast synaptic transmission mediated by glutamate.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedCasein kinase 1 delta (CK1delta) is a regulatory enzyme in the mammalian circadian oscillator and represents a potential pharmacological target for modulating circadian rhythms. Crystal structures of four different polymorphs of CK1delta have previously been determined and this article reports the crystallization and structure determination of a new crystal form belonging to space group P21. Comparison of CK1delta crystal structures reveals few conformational differences within the C-terminal lobe, but more significant movements of the beta-sheet region of the N-terminal lobe were observed. A monoclinic crystal form of casein kinase 1 delta,Zeringo NA, Murphy L, McCloskey EA, Rohal L, Bellizzi JJ 3rd Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Oct 1;69(Pt 10):1077-1083., Epub 2013 Sep 28. PMID:24100552[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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