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9QU8

apPol-DNA-nucleotide complex (ternary2)

Summary for 9QU8
Entry DOI10.2210/pdb9qu8/pdb
EMDB information53374
DescriptorPlastid replication-repair enzyme, DNA primer strand, DNA template strand, ... (4 entities in total)
Functional Keywordsdna polymerase, replication
Biological sourcePlasmodium falciparum (malaria parasite P. falciparum)
More
Total number of polymer chains3
Total formula weight95718.72
Authors
Lahiri, I.,Kumari, A. (deposition date: 2025-04-10, release date: 2025-10-29)
Primary citationKumari, A.,Enache, T.,Craggs, T.D.,Pata, J.D.,Lahiri, I.
Structural basis of multitasking by the apicoplast DNA polymerase from Plasmodium falciparum.
Nucleic Acids Res., 53:-, 2025
Cited by
PubMed Abstract: Plasmodium falciparum is a eukaryotic pathogen responsible for the majority of malaria-related fatalities. Plasmodium belongs to the phylum Apicomplexa and, like most members of this phylum, contains a non-photosynthetic plastid called the apicoplast. The apicoplast has its own genome, replicated by a dedicated replisome. Unlike other cellular replisomes, the apicoplast replisome uses a single DNA polymerase (apPol). This suggests that apPol can multitask and catalyse both replicative and lesion bypass synthesis. Replicative synthesis relies on a restrictive active site for high accuracy while lesion bypass typically requires an open active site. This raises the question: how does apPol combine the structural features of multiple DNA polymerases in a single protein? Using single-particle electron cryomicroscopy (cryoEM), we have solved the structures of apPol bound to its undamaged DNA and nucleotide substrates in five pre-chemistry conformational states. We found that apPol can accommodate a nascent base pair with the fingers in an open configuration, which might facilitate the lesion bypass activity. In the fingers-open state, we identified a nascent base pair checkpoint that preferentially selects Watson-Crick base pairs, an essential requirement for replicative synthesis. Taken together, these structural features might explain how apPol balances replicative and lesion bypass synthesis.
PubMed: 41099714
DOI: 10.1093/nar/gkaf1005
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (4.2 Å)
Structure validation

243911

数据于2025-10-29公开中

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