7PU7

DNA polymerase from M. tuberculosis

7PU7 の概要

• エントリーDOI: 10.2210/pdb7pu7/pdb
• EMDBエントリー: 13654
• 分子名称: DNA polymerase III subunit alpha, Template, primer, ... (6 entities in total)
• 機能のキーワード: inhibitor, dna polymerase, replication
• 由来する生物種: Mycobacterium tuberculosis; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 140334.19

構造登録者

Borsellini, A.,Lamers, M.H. (登録日: 2021-09-28, 公開日: 2022-02-23, 最終更新日: 2024-07-17)

主引用文献

Chengalroyen, M.D.,Mason, M.K.,Borsellini, A.,Tassoni, R.,Abrahams, G.L.,Lynch, S.,Ahn, Y.M.,Ambler, J.,Young, K.,Crowley, B.M.,Olsen, D.B.,Warner, D.F.,Barry Iii, C.E.,Boshoff, H.I.M.,Lamers, M.H.,Mizrahi, V.
DNA-Dependent Binding of Nargenicin to DnaE1 Inhibits Replication in Mycobacterium tuberculosis.
Acs Infect Dis., 8:612-625, 2022

PubMed Abstract: Natural products provide a rich source of potential antimicrobials for treating infectious diseases for which drug resistance has emerged. Foremost among these diseases is tuberculosis. Assessment of the antimycobacterial activity of nargenicin, a natural product that targets the replicative DNA polymerase of , revealed that it is a bactericidal genotoxin that induces a DNA damage response in () and inhibits growth by blocking the replicative DNA polymerase, DnaE1. Cryo-electron microscopy revealed that binding of nargenicin to DnaE1 requires the DNA substrate such that nargenicin is wedged between the terminal base pair and the polymerase and occupies the position of both the incoming nucleotide and templating base. Comparative analysis across three bacterial species suggests that the activity of nargenicin is partly attributable to the DNA binding affinity of the replicative polymerase. This work has laid the foundation for target-led drug discovery efforts focused on DnaE1.

PubMed: 35143160
DOI: 10.1021/acsinfecdis.1c00643

実験手法

ELECTRON MICROSCOPY (2.9 Å)