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Functional and phylogenetic evidence of a bacterial origin for the first enzyme in sphingolipid biosynthesis in a phylum of eukaryotic protozoan parasites

Mina, John; Thye, Julie; Alqaisi, Amjed; Bird, Louise; Dods, Robert; Groftehauge, Morten; Mosely, Jackie; Pratt, Steven; Shams-Eldin, Hosam; Schwarz, Ralph; Pohl, Ehmke; Denny, Paul W.

Functional and phylogenetic evidence of a bacterial origin for the first enzyme in sphingolipid biosynthesis in a phylum of eukaryotic protozoan parasites Thumbnail


Authors

Julie Thye

Amjed Alqaisi

Louise Bird

Robert Dods

Morten Groftehauge

Jackie Mosely

Steven Pratt

Hosam Shams-Eldin

Ralph Schwarz



Abstract

Toxoplasma gondii is an obligate, intracellular eukaryotic apicomplexan protozoan parasite that can cause fetal damage and abortion in both animals and humans. Sphingolipids are essential and ubiquitous components of eukaryotic membranes that are both synthesized and scavenged by the Apicomplexa. Here we report the identification, isolation and analyses of the Toxoplasma serine palmitoyltransferase, an enzyme catalyzing the first and rate-limiting step in sphingolipid biosynthesis - the condensation of serine and palmitoyl-CoA. In all eukaryotes analyzed to date, serine palmitoyltransferase is a highly conserved heterodimeric enzyme complex. However, biochemical and structural analyses demonstrated the apicomplexan orthologue to be a functional, homodimeric serine palmitoyltransferase localized to the endoplasmic reticulum. Furthermore, phylogenetic studies indicated that it was evolutionarily related to the prokaryotic serine palmitoyltransferase, identified in the Sphingomonadaceae as a soluble homodimeric enzyme. Therefore this enzyme, conserved throughout the Apicomplexa, is likely to have been obtained via lateral gene transfer from a prokaryote. Importantly, the structural and evolutionary divergence of the apicomplexan serine palmitoyltransferase suggests that it might have significant potential as a drug target.

Citation

Mina, J., Thye, J., Alqaisi, A., Bird, L., Dods, R., Groftehauge, M., …Denny, P. W. (2017). Functional and phylogenetic evidence of a bacterial origin for the first enzyme in sphingolipid biosynthesis in a phylum of eukaryotic protozoan parasites. Journal of Biological Chemistry, 292(29), 12208-12219. https://doi.org/10.1074/jbc.m117.792374

Journal Article Type Article
Acceptance Date Jun 2, 2017
Online Publication Date Jun 2, 2017
Publication Date Jul 21, 2017
Deposit Date Apr 11, 2017
Publicly Available Date Mar 29, 2024
Journal Journal of Biological Chemistry
Print ISSN 0021-9258
Electronic ISSN 1083-351X
Publisher American Society for Biochemistry and Molecular Biology
Peer Reviewed Peer Reviewed
Volume 292
Issue 29
Pages 12208-12219
DOI https://doi.org/10.1074/jbc.m117.792374

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