Cryo-EM Structures of the Plasmodium falciparum Apicoplast DNA Polymerase.

ABSTRACT: The apicoplast DNA polymerase (apPol) from Plasmodium falciparum is essential for the parasite's survival, making it a prime target for antimalarial therapies. Here, we present cryo-electron microscopy structures of the apPol in complex with DNA and incoming nucleotide, offering insights into its molecular mechanisms. Our structural analysis reveals that apPol contains critical residues for high-fidelity DNA synthesis, but lacks certain structural elements to confer processive DNA synthesis during replication, suggesting the presence of additional accessory factors. The enzyme exhibits large-scale conformational changes upon DNA and nucleotide binding, particularly within the fingers and thumb subdomains. These movements reveal potential allosteric sites that could serve as targets for dru

SUBMITTER: Lo CY 

PROVIDER: S-EPMC12060727 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature