PDBsum entry 4f9c

Transferase/transferase inhibitor

PDB id: 4f9c

Contents

Protein chains

306 a.a.

88 a.a.

Ligands

0SX

Metals

_ZN

Waters ×81

PDB id:

4f9c

Name:

Transferase/transferase inhibitor

Title:

Human cdc7 kinase in complex with dbf4 and xl413

Structure:

Cell division cycle 7-related protein kinase. Chain: a. Synonym: cdc7-related kinase, hscdc7, hucdc7. Engineered: yes. Protein dbf4 homolog a. Chain: b. Synonym: activator of s phase kinase, chiffon homolog a, dbf4-type zinc finger-containing protein 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cdc7, cdc7l1. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: ask, dbf4, dbf4a, zdbf1.

Resolution:

2.08Å R-factor: 0.206 R-free: 0.249

Authors:

S.Hughes,P.Cherepanov

Key ref:

S.Hughes et al. (2012). Crystal structure of human CDC7 kinase in complex with its activator DBF4. Nat Struct Biol, 19, 1101-1107. PubMed id: 23064647

Date:

18-May-12 Release date: 31-Oct-12

Protein chain

O00311  (CDC7_HUMAN) -  Cell division cycle 7-related protein kinase from Homo sapiens

Seq: 574 a.a.

Struc: 306 a.a.

Protein chain

Q9UBU7  (DBF4A_HUMAN) -  Protein DBF4 homolog A from Homo sapiens

Seq: 674 a.a.

Struc: 88 a.a.

Enzyme reactions

• Enzyme class 2: Chain A: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] (Bound ligand (Het Group name = 0SX) matches with 42.42% similarity) + ADP + H(+)

L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] (Bound ligand (Het Group name = 0SX) matches with 42.42% similarity) + ADP + H(+)

• Enzyme class 3: Chain B: E.C.?

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Nat Struct Biol 19:1101-1107 (2012)

PubMed id: 23064647

Crystal structure of human CDC7 kinase in complex with its activator DBF4.

S.Hughes, F.Elustondo, A.Di Fonzo, F.G.Leroux, A.C.Wong, A.P.Snijders, S.J.Matthews, P.Cherepanov.

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.