Crystal structure of sphingosine kinase 1 with PF-543

Jing Wang; Stefan Knapp; Nigel J. Pyne; Susan Pyne; Jonathan M. Elkins

doi:10.1021/ml5004074

Crystal structure of sphingosine kinase 1 with PF-543

Jing Wang, Stefan Knapp, Nigel J. Pyne, Susan Pyne, Jonathan M. Elkins

Strathclyde Institute Of Pharmacy And Biomedical Sciences

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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

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10.1021/ml5004074Licence: CC BY 3.0

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

Cite this

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title = "Crystal structure of sphingosine kinase 1 with PF-543",

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 {\AA} 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.",

keywords = "SPHK1, PF-543, SPHK2, sphingosine, lipid, S1P",

author = "Jing Wang and Stefan Knapp and Pyne, {Nigel J.} and Susan Pyne and Elkins, {Jonathan M.}",

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T1 - Crystal structure of sphingosine kinase 1 with PF-543

AU - Wang, Jing

AU - Knapp, Stefan

AU - Pyne, Nigel J.

AU - Pyne, Susan

AU - Elkins, Jonathan M.

PY - 2014/12/27

Y1 - 2014/12/27

N2 - 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.

AB - 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.

KW - SPHK1

KW - PF-543

KW - SPHK2

KW - sphingosine

KW - lipid

KW - S1P

U2 - 10.1021/ml5004074

DO - 10.1021/ml5004074

M3 - Article

SN - 1948-5875

VL - 5

SP - 1329

EP - 1333

JO - Medicinal Chemistry Letters

JF - Medicinal Chemistry Letters

IS - 12

ER -

Crystal structure of sphingosine kinase 1 with PF-543

Abstract

Keywords

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