6RB4

Crystal structure of the Pri1 subunit of human primase

6RB4 の概要

• エントリーDOI: 10.2210/pdb6rb4/pdb
• 関連するPDBエントリー: 6R4S 6R4T 6R4U 6R5D 6R5E
• 分子名称: DNA primase small subunit, 1,2-ETHANEDIOL, ZINC ION, ... (4 entities in total)
• 機能のキーワード: primase, dna-dependent rna polymerase, atp, priming, replication
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 49034.20

構造登録者

Kilkenny, M.L.,Pellegrini, L. (登録日: 2019-04-09, 公開日: 2019-09-11, 最終更新日: 2024-01-24)

主引用文献

Holzer, S.,Rzechorzek, N.J.,Short, I.R.,Jenkyn-Bedford, M.,Pellegrini, L.,Kilkenny, M.L.
Structural Basis for Inhibition of Human Primase by Arabinofuranosyl Nucleoside Analogues Fludarabine and Vidarabine.
Acs Chem.Biol., 14:1904-1912, 2019

PubMed Abstract: Nucleoside analogues are widely used in clinical practice as chemotherapy drugs. Arabinose nucleoside derivatives such as fludarabine are effective in the treatment of patients with acute and chronic leukemias and non-Hodgkin's lymphomas. Although nucleoside analogues are generally known to function by inhibiting DNA synthesis in rapidly proliferating cells, the identity of their targets and mechanism of action are often not known in molecular detail. Here we provide a structural basis for arabinose nucleotide-mediated inhibition of human primase, the DNA-dependent RNA polymerase responsible for initiation of DNA synthesis in DNA replication. Our data suggest ways in which the chemical structure of fludarabine could be modified to improve its specificity and affinity toward primase, possibly leading to less toxic and more effective therapeutic agents.

PubMed: 31479243
DOI: 10.1021/acschembio.9b00367

実験手法

X-RAY DIFFRACTION (1.5 Å)