6YA7

Cdc7-Dbf4 bound to an Mcm2-S40 derived bivalent substrate

6YA7 の概要

• エントリーDOI: 10.2210/pdb6ya7/pdb
• 分子名称: Cell division cycle 7-related protein kinase,Cell division cycle 7-related protein kinase,Cell division cycle 7-related protein kinase, Protein DBF4 homolog A, DNA replication licensing factor MCM2, ... (6 entities in total)
• 機能のキーワード: kinase, cdc7, dbf4, cell cycle, bivalent substrate, transferase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 59509.41

構造登録者

Dick, S.D.,Cherepanov, P. (登録日: 2020-03-11, 公開日: 2020-05-27, 最終更新日: 2024-01-24)

主引用文献

Dick, S.D.,Federico, S.,Hughes, S.M.,Pye, V.E.,O'Reilly, N.,Cherepanov, P.
Structural Basis for the Activation and Target Site Specificity of CDC7 Kinase.
Structure, 28:954-962.e4, 2020

PubMed Abstract: CDC7 is an essential Ser/Thr kinase that acts upon the replicative helicase throughout the S phase of the cell cycle and is activated by DBF4. Here, we present crystal structures of a highly active human CDC7-DBF4 construct. The structures reveal a zinc-finger domain at the end of the kinase insert 2 that pins the CDC7 activation loop to motif M of DBF4 and the C lobe of CDC7. These interactions lead to ordering of the substrate-binding platform and full opening of the kinase active site. In a co-crystal structure with a mimic of MCM2 Ser40 phosphorylation target, the invariant CDC7 residues Arg373 and Arg380 engage phospho-Ser41 at substrate P+1 position, explaining the selectivity of the S-phase kinase for Ser/Thr residues followed by a pre-phosphorylated or an acidic residue. Our results clarify the role of DBF4 in activation of CDC7 and elucidate the structural basis for recognition of its preferred substrates.

PubMed: 32521228
DOI: 10.1016/j.str.2020.05.010

実験手法

X-RAY DIFFRACTION (1.67 Å)