3'-5' exonuclease activity / DNA replication / DNA-directed DNA polymerase / DNA-directed DNA polymerase activity / cytoplasm 類似検索 - 分子機能
Bacterial DNA polymerase III alpha subunit, thumb domain / DNA polymerase III, alpha subunit / Bacterial DNA polymerase III, alpha subunit, NTPase domain / DNA polymerase, helix-hairpin-helix motif / DNA polymerase III alpha subunit finger domain / Bacterial DNA polymerase III alpha NTPase domain / Helix-hairpin-helix motif / Bacterial DNA polymerase III alpha subunit finger domain / PHP domain / PHP domain ...Bacterial DNA polymerase III alpha subunit, thumb domain / DNA polymerase III, alpha subunit / Bacterial DNA polymerase III, alpha subunit, NTPase domain / DNA polymerase, helix-hairpin-helix motif / DNA polymerase III alpha subunit finger domain / Bacterial DNA polymerase III alpha NTPase domain / Helix-hairpin-helix motif / Bacterial DNA polymerase III alpha subunit finger domain / PHP domain / PHP domain / Polymerase/histidinol phosphatase, N-terminal / DNA polymerase alpha chain like domain / Polymerase/histidinol phosphatase-like 類似検索 - ドメイン・相同性
ジャーナル: ACS Infect Dis / 年: 2022 タイトル: DNA-Dependent Binding of Nargenicin to DnaE1 Inhibits Replication in . 著者: Melissa D Chengalroyen / Mandy K Mason / Alessandro Borsellini / Raffaella Tassoni / Garth L Abrahams / Sasha Lynch / Yong-Mo Ahn / Jon Ambler / Katherine Young / Brendan M Crowley / David B ...著者: Melissa D Chengalroyen / Mandy K Mason / Alessandro Borsellini / Raffaella Tassoni / Garth L Abrahams / Sasha Lynch / Yong-Mo Ahn / Jon Ambler / Katherine Young / Brendan M Crowley / David B Olsen / Digby F Warner / Clifton E Barry Iii / Helena I M Boshoff / Meindert H Lamers / Valerie Mizrahi / 要旨: 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 ...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.