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Publication Abstract from PubMed

In free-living and parasitic nematodes, the methylation of phosphoethanolamine to phosphocholine provides a key metabolite to sustain phospholipid biosynthesis for growth and development. Because the phosphoethanolamine methyltransferases (PMT) of nematodes are essential for normal growth and development, these enzymes are potential targets of inhibitor design. The pine wilt nematode (Bursaphelenchus xylophilus) causes extensive damage to trees used for lumber and paper in Asia. As a first step toward testing BxPMT1 as a potential nematicide target, we determined the 2.05 A resolution x-ray crystal structure of the enzyme as a dead-end complex with phosphoethanolamine and S-adenosylhomocysteine. The three-dimensional structure of BxPMT1 served as a template for site-directed mutagenesis to probe the contribution of active site residues to catalysis and phosphoethanolamine binding using steady-state kinetic analysis. Biochemical analysis of the mutants identifies key residues on the beta1d-alpha6 loop (W123F, M126I, and Y127F) and beta1e-alpha7 loop (S155A, S160A, H170A, T178V, and Y180F) that form the phosphobase binding site and suggest that Tyr127 facilitates the methylation reaction in BxPMT1.

Structural and biochemical analysis of phosphoethanolamine methyltransferase from the pine wilt nematode Bursaphelenchus xylophilus.,Lee SG, Chung MS, DeMarsilis AJ, Holland CK, Jaswaney RV, Jiang C, Kroboth JHP, Kulshrestha K, Marcelo RZW, Meyyappa VM, Nelson GB, Patel JK, Petronio AJ, Powers SK, Qin PR, Ramachandran M, Rayapati D, Rincon JA, Rocha A, Ferreira JGRN, Steinbrecher MK, Yao K, Zhang EJ, Zou AJ, Gang M, Sparks M, Cascella B, Cruz W, Jez JM Mol Biochem Parasitol. 2020 May 30;238:111291. doi:, 10.1016/j.molbiopara.2020.111291. PMID:32479776^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.