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Exploring Leishmania major inositol phosphorylceramide synthase (LmjIPCS): insights into the ceramide binding domain

Mina, J.G.; Mosely, J.A.; Ali, H.Z.; Denny, P.W.; Steel, P.G.

Exploring Leishmania major inositol phosphorylceramide synthase (LmjIPCS): insights into the ceramide binding domain Thumbnail


Authors

J.A. Mosely

H.Z. Ali

P.G. Steel



Abstract

The synthesis of set of ceramide analogues exploring hydrophobicity in the acyl chains and the degree and nature of hydroxylation is described. These have been assayed against the parasitic protozoan enzyme LmjIPCS. These studies showed that whilst the C-3 hydroxyl group was not essential for turnover it provided enhanced affinity. Reflecting the membrane bound nature of the enzyme a long (C13) hydrocarbon ceramide tail was necessary for both high affinity and turnover. Whilst the N-acyl chain also contributed to affinity, analogues lacking the amide linkage functioned as competitive inhibitors in both enzyme and cell-based assays. A model that accounts for this observation is proposed.

Citation

Mina, J., Mosely, J., Ali, H., Denny, P., & Steel, P. (2011). Exploring Leishmania major inositol phosphorylceramide synthase (LmjIPCS): insights into the ceramide binding domain. Organic and Biomolecular Chemistry, 9(6), 1823-1830. https://doi.org/10.1039/c0ob00871k

Journal Article Type Article
Acceptance Date Dec 13, 2010
Online Publication Date Jan 26, 2011
Publication Date Mar 21, 2011
Deposit Date Mar 3, 2011
Publicly Available Date Mar 29, 2024
Journal Organic and Biomolecular Chemistry
Print ISSN 1477-0520
Electronic ISSN 1477-0539
Publisher Royal Society of Chemistry
Peer Reviewed Peer Reviewed
Volume 9
Issue 6
Pages 1823-1830
DOI https://doi.org/10.1039/c0ob00871k

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