Crystal structure of sphingosine kinase 1 with PF-543

Jing Wang; Stefan Knapp; Nigel Pyne; Susan Pyne; Jonathan Elkins

doi:10.1021/ml5004074

Crystal structure of sphingosine kinase 1 with PF-543

Jing Wang, Stefan Knapp, Nigel Pyne, Susan Pyne, Jonathan Elkins

Strathclyde Institute Of Pharmacy And Biomedical Sciences

Research output: Contribution to journal › Article

50 Citations (Scopus)

90 Downloads (Pure)

Abstract

The most potent inhibitor of Sphingosine Kinase 1 (SPHK1) so far identified is PF-543. The crystal structure of SPHK1 in complex with inhibitor PF-543 to 1.8 Å resolution reveals the inhibitor bound in a bent conformation analogous to that expected of a bound sphingosine substrate but with a rotated head group. The structural data presented will aid in the design of SPHK1 and SPHK2 inhibitors with improved properties.

Original language	English
Pages (from-to)	1329-1333
Number of pages	5
Journal	Medicinal Chemistry Letters
Volume	5
Issue number	12
Early online date	27 Oct 2014
DOIs	https://doi.org/10.1021/ml5004074
Publication status	Published - 27 Dec 2014

Keywords

SPHK1
PF-543
SPHK2
sphingosine
lipid
S1P

Access to Document

10.1021/ml5004074

Wang-etal-MCL-2014-Crystal-structure-of-Sphingosine-Kinase
This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited.
Final published version, 3.74 MBLicence: CC BY 4.0

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Profiles

Nigel Pyne

n.j.pyne@strath.ac.uk

Strathclyde Institute Of Pharmacy And Biomedical Sciences - Professor

Person: Academic

Susan Pyne

susan.pyne@strath.ac.uk

Strathclyde Institute Of Pharmacy And Biomedical Sciences - Professor

Person: Academic

Cite this

Wang, J., Knapp, S., Pyne, N., Pyne, S., & Elkins, J. (2014). Crystal structure of sphingosine kinase 1 with PF-543. Medicinal Chemistry Letters, 5(12), 1329-1333. https://doi.org/10.1021/ml5004074

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AU - Elkins, Jonathan

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KW - S1P

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