4F9C

Human CDC7 kinase in complex with DBF4 and XL413

Summary for 4F9C

• Entry DOI: 10.2210/pdb4f9c/pdb
• Related: 4F99 4F9A 4F9B
• Descriptor: Cell division cycle 7-related protein kinase, Protein DBF4 homolog A, 8-chloro-2-[(2S)-pyrrolidin-2-yl][1]benzofuro[3,2-d]pyrimidin-4(3H)-one, ... (5 entities in total)
• Functional Keywords: ser/thr protein kinase, transferase, phosphorylation, cell cycle, cell division, mitosis, s phase, serine/threonine-protein kinase, dbf4-dependent kinase, ddk, atp-binding, nucleotide-binding, zinc-binding, nucleus, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: O00311 Q9UBU7
• Total number of polymer chains: 2
• Total formula weight: 57912.37

Authors

Hughes, S.,Cherepanov, P. (deposition date: 2012-05-18, release date: 2012-10-31, Last modification date: 2024-02-28)

Primary citation

Hughes, S.,Elustondo, F.,Di Fonzo, A.,Leroux, F.G.,Wong, A.C.,Snijders, A.P.,Matthews, S.J.,Cherepanov, P.
Crystal structure of human CDC7 kinase in complex with its activator DBF4.
Nat.Struct.Mol.Biol., 19:1101-1107, 2012

PubMed Abstract: 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 Å(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 αC 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.

PubMed: 23064647
DOI: 10.1038/nsmb.2404

Experimental method

X-RAY DIFFRACTION (2.08 Å)