5LUQ

Crystal Structure of Human DNA-dependent Protein Kinase Catalytic Subunit (DNA-PKcs)

5LUQ の概要

• エントリーDOI: 10.2210/pdb5luq/pdb
• 分子名称: DNA-dependent protein kinase catalytic subunit,DNA-dependent Protein Kinase Catalytic Subunit,DNA-dependent protein kinase catalytic subunit, C-terminal fragment of KU80 (KU80ct194) (2 entities in total)
• 機能のキーワード: dna-pkcs, kinase, dna repair, nhej, double strand break repair, heat repeat, transferase
• 由来する生物種: Homo sapiens; 詳細
• 細胞内の位置: Nucleus : P78527
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 972480.57

構造登録者

Sibanda, B.L.,Chirgadze, D.Y.,Ascher, D.B.,Blundell, T.L. (登録日: 2016-09-09, 公開日: 2017-02-15, 最終更新日: 2024-10-23)

主引用文献

Sibanda, B.L.,Chirgadze, D.Y.,Ascher, D.B.,Blundell, T.L.
DNA-PKcs structure suggests an allosteric mechanism modulating DNA double-strand break repair.
Science, 355:520-524, 2017

PubMed Abstract: DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is a central component of nonhomologous end joining (NHEJ), repairing DNA double-strand breaks that would otherwise lead to apoptosis or cancer. We have solved its structure in complex with the C-terminal peptide of Ku80 at 4.3 angstrom resolution using x-ray crystallography. We show that the 4128-amino acid structure comprises three large structural units: the N-terminal unit, the Circular Cradle, and the Head. Conformational differences between the two molecules in the asymmetric unit are correlated with changes in accessibility of the kinase active site, which are consistent with an allosteric mechanism to bring about kinase activation. The location of KU80ct in the vicinity of the breast cancer 1 (BRCA1) binding site suggests competition with BRCA1, leading to pathway selection between NHEJ and homologous recombination.

PubMed: 28154079
DOI: 10.1126/science.aak9654

実験手法

X-RAY DIFFRACTION (4.3 Å)