9CAY

Ternary structure of Plasmodium falciparum apicoplast DNA polymerase (exo-minus)

9CAY の概要

• エントリーDOI: 10.2210/pdb9cay/pdb
• EMDBエントリー: 45407
• 分子名称: DNA (5'-D(P*CP*AP*GP*CP*TP*CP*TP*AP*CP*GP*GP*AP*TP*GP*CP*CP*TP*CP*AP*CP*A)-3'), Plastid replication-repair enzyme, DNA (5'-D(*AP*TP*GP*TP*GP*AP*GP*GP*CP*AP*TP*CP*CP*GP*TP*AP*GP*(2DA))-3'), ... (5 entities in total)
• 機能のキーワード: dna polymerase, dna binding protein, dna binding protein-dna complex, dna binding protein/dna
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 89597.12

構造登録者

Lo, C.-Y.,Gao, Y. (登録日: 2024-06-18, 公開日: 2024-11-06, 最終更新日: 2025-06-04)

主引用文献

Lo, C.Y.,Ung, A.R.,Koley, T.,Nelson, S.W.,Gao, Y.
Cryo-EM Structures of the Plasmodium falciparum Apicoplast DNA Polymerase.
J.Mol.Biol., 436:168842-168842, 2024

PubMed 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 drug design. Our findings provide a foundation for advancing the understanding of apPol's unique functional mechanisms and potentially offering new avenues for the development of novel inhibitors and therapeutic interventions against malaria.

PubMed: 39490679
DOI: 10.1016/j.jmb.2024.168842

実験手法

ELECTRON MICROSCOPY (3.17 Å)