Crystal structure of phosphoethanolamine methyltransferase from Plasmodium falciparum in complex with amodiaquine.

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Lee SG, Alpert TD, Jez JM

Crystal structure of phosphoethanolamine methyltransferase from Plasmodium falciparum in complex with amodiaquine.

Bioorg Med Chem Lett. 2012 Aug 1;22(15):4990-3. doi: 10.1016/j.bmcl.2012.06.032. Epub 2012 Jun 17.

PubMed ID

22771008 [ View in PubMed

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Abstract

Phosphoethanolamine N-methyltransferase (PMT) is essential for phospholipid biogenesis in the malarial parasite Plasmodium falciparum. PfPMT catalyzes the triple methylation of phosphoethanolamine to produce phosphocholine, which is then used for phosphatidylcholine synthesis. Here we describe the 2.0A resolution X-ray crystal structure of PfPMT in complex with amodiaquine. To better characterize inhibition of PfPMT by amodiaquine, we determined the IC(50) values of a series of aminoquinolines using a direct radiochemical assay. Both structural and functional analyses provide a possible approach for the development of new small molecule inhibitors of PfPMT.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Amodiaquine	Histamine N-methyltransferase	Ki (nM)	19	N/A	N/A	Details