5DKT

N-terminal His tagged apPOL exonuclease mutant

Summary for 5DKT

• Entry DOI: 10.2210/pdb5dkt/pdb
• Related: 5DKU
• Descriptor: Prex DNA polymerase, SULFATE ION, SODIUM ION, ... (4 entities in total)
• Functional Keywords: dna polymerase, transferase
• Biological source: Plasmodium falciparum
• Total number of polymer chains: 1
• Total formula weight: 77061.81

Authors

Milton, M.E.,Honzatko, R.B.,Choe, J.Y.,Nelson, S.W. (deposition date: 2015-09-04, release date: 2016-08-10, Last modification date: 2023-09-27)

Primary citation

Milton, M.E.,Choe, J.Y.,Honzatko, R.B.,Nelson, S.W.
Crystal Structure of the Apicoplast DNA Polymerase from Plasmodium falciparum: The First Look at a Plastidic A-Family DNA Polymerase.
J.Mol.Biol., 428:3920-3934, 2016

PubMed Abstract: Plasmodium falciparum, the primary cause of malaria, contains a non-photosynthetic plastid called the apicoplast. The apicoplast exists in most members of the phylum Apicomplexa and has its own genome along with organelle-specific enzymes for its replication. The only DNA polymerase found in the apicoplast (apPOL) was putatively acquired through horizontal gene transfer from a bacteriophage and is classified as an atypical A-family polymerase. Here, we present its crystal structure at a resolution of 2.9Å. P. falciparum apPOL, the first structural representative of a plastidic A-family polymerase, diverges from typical A-family members in two of three previously identified signature motifs and in a region not implicated by sequence. Moreover, apPOL has an additional N-terminal subdomain, the absence of which severely diminishes its 3' to 5' exonuclease activity. A compound known to be toxic to Plasmodium is a potent inhibitor of apPOL, suggesting that apPOL is a viable drug target. The structure provides new insights into the structural diversity of A-family polymerases and may facilitate structurally guided antimalarial drug design.

PubMed: 27487482
DOI: 10.1016/j.jmb.2016.07.016

Experimental method

X-RAY DIFFRACTION (2.9 Å)