4f99

Human CDC7 kinase in complex with DBF4 and nucleotide

spinqualitylabelsall models 4f99, resolution 2.33Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4f99 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: ADP, MG, ZN Related: 4f9a, 4f9b, 4f9c, 3pvg Gene: CDC7, CDC7L1 (Homo sapiens), ASK, DBF4, DBF4A, ZDBF1 (Homo sapiens) Activity: Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 Resources: FirstGlance, OCA, RCSB, PDBsum Function [DBF4A_HUMAN] Regulatory subunit for CDC7 which activates its kinase activity thereby playing a central role in DNA replication and cell proliferation. Required for progression of S phase. The complex CDC7-DBF4A selectively phosphorylates MCM2 subunit at 'Ser-40' and 'Ser-53' and then is involved in regulating the initiation of DNA replication during cell cycle. Publication Abstract from PubMed CDC7 is a serine/threonine kinase that is essential for the initiation of eukaryotic DNA replication. CDC7 activity is controlled by its activator, DBF4. Here we present crystal structures of human CDC7-DBF4 in complex with a nucleotide or ATP-competing small molecules, revealing the active and inhibited forms of the kinase, respectively. DBF4 wraps around CDC7, burying approximately 6,000 A(2) of hydrophobic molecular surface in a bipartite interface. The effector domain of DBF4, containing conserved motif C, is essential and sufficient to support CDC7 kinase activity by binding to the kinase N-terminal lobe and stabilizing its canonical alphaC helix. DBF4 motif M latches onto the C-terminal lobe of the kinase, acting as a tethering domain. Our results elucidate the structural basis for binding to and activation of CDC7 by DBF4 and provide a framework for the design of more potent and specific CDC7 inhibitors. Crystal structure of human CDC7 kinase in complex with its activator DBF4.,Hughes S, Elustondo F, Di Fonzo A, Leroux FG, Wong AC, Snijders AP, Matthews SJ, Cherepanov P Nat Struct Mol Biol. 2012 Nov;19(11):1101-7. doi: 10.1038/nsmb.2404. Epub 2012, Oct 14. PMID:23064647 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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