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

Journal Article · Tue Jul 17 00:00:00 EDT 2012 · Bioorganic and Medicinal Chemistry Letters

DOI:https://doi.org/10.1016/j.bmcl.2012.06.032· OSTI ID:1046240

Lee, Soon Goo; Alpert, Tara D; Jez, Joseph M ^[1]

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1. WU

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 2.0 {angstrom} resolution X-ray crystal structure of PfPMT in complex with amodiaquine. To better characterize inhibition of PfPMT by amodiaquine, we determined the IC{sub 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.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: NIAID
• OSTI ID: 1046240
• Journal Information: Bioorganic and Medicinal Chemistry Letters, Journal Name: Bioorganic and Medicinal Chemistry Letters Journal Issue: 15 Vol. 22; ISSN 0960-894X
• Country of Publication: United States
• Language: ENGLISH

Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
CRYSTAL STRUCTURE
INHIBITION
LECITHINS
MALARIA
METHYLATION
MOLECULES
PARASITES
PHOSPHOLIPIDS
PLASMODIUM
RESOLUTION
SYNTHESIS