Phosphoethanolamine N-methyltransferase (Pmt-1) Catalyses the First Reaction of a New Pathway for Phosphocholine Biosynthesis in Caenorhabditis Elegans.
From: Divergence, Inc., 893 North Warson Rd, St. Louis, MO 63141, USA.
The Biochemical journal
- Publish Date: Jun 2007
- ISSN: 1470-8728
- Volume: 404
- Issue: 3
- Pages: 439-48
- Medium: Internet
- Language: English
- Citation (JAMA): Brendza Katherine M, Haakenson William, Cahoon Rebecca E, et al. Phosphoethanolamine N-methyltransferase (Pmt-1) Catalyses the First Reaction of a New Pathway for Phosphocholine Biosynthesis in Caenorhabditis Elegans.. Biochem. J. Jun 2007;404:439-48
Abstract
The development of nematicides targeting parasitic nematodes of animals and plants requires the identification of biochemical targets not found in host organisms. Recent studies suggest that Caenorhabditis elegans synthesizes phosphocholine through the action of PEAMT (S-adenosyl-L-methionine:phosphoethanolamine N-methyltransferases) that convert phosphoethanolamine into phosphocholine. Here, we examine the function of a PEAMT from C. elegans (gene: pmt-1; protein: PMT-1). Our analysis shows that PMT-1 only catalyses the conversion of phosphoethanolamine into phospho-monomethylethanolamine, which is the first step in the PEAMT pathway. This is in contrast with the multifunctional PEAMT from plants and Plasmodium that perform multiple methylations in the pathway using a single enzyme. Initial velocity and product inhibition studies indicate that PMT-1 uses a random sequential kinetic mechanism and is feedback inhibited by phosphocholine. To examine the effect of abrogating PMT-1 activity in C. elegans, RNAi (RNA interference) experiments demonstrate that pmt-1 is required for worm growth and development and validate PMT-1 as a potential target for inhibition. Moreover, providing pathway metabolites downstream of PMT-1 reverses the RNAi phenotype of pmt-1. Because PMT-1 is not found in mammals, is only distantly related to the plant PEAMT and is conserved in multiple parasitic nematodes of humans, animals and crop plants, inhibitors targeting it may prove valuable in human and veterinary medicine and agriculture.
Mesh Headings (Keywords): Amino Acid Sequence, Animals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Humans, Methyltransferases, Molecular Sequence Data, Phenotype, Phosphatidylcholines, Plant Proteins, RNA Interference, Sequence Alignment, Substrate Specificity
Check for Full Text / PubMed Unique Identifier (PMID): 17313371
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