6CST

Structure of human DNA polymerase kappa with DNA

6CST の概要

• エントリーDOI: 10.2210/pdb6cst/pdb
• 分子名称: DNA polymerase kappa, CHLORIDE ION, POTASSIUM ION, ... (12 entities in total)
• 機能のキーワード: dna polymerase kappa, translesion synthesis, dna replication, replication, transferase-dna complex, transferase/dna
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 143550.95

構造登録者

Jha, V.,Ling, H. (登録日: 2018-03-21, 公開日: 2019-01-30, 最終更新日: 2024-03-13)

主引用文献

Jha, V.,Ling, H.
2.0 angstrom resolution crystal structure of human pol kappa reveals a new catalytic function of N-clasp in DNA replication.
Sci Rep, 8:15125-15125, 2018

PubMed Abstract: Human polymerase kappa (polκ) is a distinct Y-family DNA polymerase with a unique N-terminal N-clasp domain. The N-clasp renders polκ's high efficiency and accuracy in DNA replication and lesion bypass. How N-clasp empowers polκ in replication remains unclear due to the disordering of N-clasp. Here, we present a 2.0-Å resolution crystal structure of a polκ ternary complex with DNA and an incoming nucleotide. The structure-function study reveals an ordered N-clasp domain that brings conserved and functionally important residues in contact with the replicating basepair in the active site and contributes to the nucleotidyl transfer reaction. Particularly, a fully ordered Lys25 from the N-clasp domain is in H-bonding with the α- and γ-phosphates of the incoming nucleotide. K25A mutation reduces the polymerase activity of polκ significantly. This lysine is structurally analogous to a conserved lysine in the A-family DNA polymerases in the closed form. In contrast, Lys25 in the previous structures of polκ does not have any contacts with the incoming nucleotide, resembling an open form of a DNA polymerase. Based on structural and functional similarity, we propose a local open/closed mechanism for polκ in DNA replication catalysis, which mimics the common mechanism for all DNA polymerases.

PubMed: 30310122
DOI: 10.1038/s41598-018-33371-5

実験手法

X-RAY DIFFRACTION (2 Å)