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.

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: Dec 13, 2011
• 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
• Public URL: https://durham-repository.worktribe.com/output/1511746