DNA-Dependent Binding of Nargenicin to DnaE1 Inhibits Replication in <i>Mycobacterium tuberculosis</i>.

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 Staphylococcus aureus, revealed that it is a bactericidal genotoxin that induces a DNA damage response in Mycobacterium tuberculosis (Mtb) and inhibits growth by blocking the replicative DNA polymerase, DnaE1. Cryo-electron microscopy revealed that binding of nargenicin to Mtb 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 templat

SUBMITTER: Chengalroyen MD 

PROVIDER: S-EPMC8922275 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature