5dkt
N-terminal His tagged apPOL exonuclease mutantN-terminal His tagged apPOL exonuclease mutant
Structural highlights
FunctionPublication Abstract from PubMedPlasmodium 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 2.9A. 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. Crystal Structure of the Apicoplast DNA Polymerase from Plasmodium falciparum: The First Look at a Plastidic A-Family DNA Polymerase.,Milton ME, Choe JY, Honzatko RB, Nelson SW J Mol Biol. 2016 Jul 31. pii: S0022-2836(16)30274-1. doi:, 10.1016/j.jmb.2016.07.016. PMID:27487482[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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