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 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.
authors.affiliation: Structural Genomics Consortium, University of Oxford , Old Road Campus Research Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, U.K.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Structural Genomics Consortium, University of Oxford , Old Road Campus Research Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, U.K. ; Target Discovery Institute, University of Oxford , NDM Research Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7FZ, U.K.
authors.forename: Stefan
authors.initials: S
authors.lastname: Knapp
authors.affiliation: Cell Biology Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde , Glasgow G4 0RE, U.K.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Pyne
authors.affiliation: Cell Biology Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde , Glasgow G4 0RE, U.K.
authors.forename: Susan
authors.initials: S
authors.lastname: Pyne
authors.affiliation: Structural Genomics Consortium, University of Oxford , Old Road Campus Research Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, U.K.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Elkins
keywords: PF-543; S1P; SPHK1; SPHK2; lipid; sphingosine