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http://purl.uniprot.org/citations/23602659http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23602659http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23602659http://www.w3.org/2000/01/rdf-schema#comment"Sphingosine kinase 1 (SphK1) is a lipid kinase that catalyzes the conversion of sphingosine to sphingosine-1-phosphate (S1P), which has been shown to play a role in lymphocyte trafficking, angiogenesis, and response to apoptotic stimuli. As a central enzyme in modulating the S1P levels in cells, SphK1 emerges as an important regulator for diverse cellular functions and a potential target for drug discovery. Here, we present the crystal structures of human SphK1 in the apo form and in complexes with a substrate sphingosine-like lipid, ADP, and an inhibitor at 2.0-2.3 Å resolution. The SphK1 structures reveal a two-domain architecture in which its catalytic site is located in the cleft between the two domains and a hydrophobic lipid-binding pocket is buried in the C-terminal domain. Comparative analysis of these structures with mutagenesis and kinetic studies provides insight into how SphK1 recognizes the lipid substrate and catalyzes ATP-dependent phosphorylation."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.org/dc/terms/identifier"doi:10.1016/j.str.2013.02.025"xsd:string
http://purl.uniprot.org/citations/23602659http://purl.org/dc/terms/identifier"doi:10.1016/j.str.2013.02.025"xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"Liu J."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"Liu J."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"Xu H."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"Xu H."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"Wang Z."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"Wang Z."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"Dai J."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"Dai J."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"Min X."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"Min X."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"Walker N."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"Walker N."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"Xiao S.H."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"Xiao S.H."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"An S."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"An S."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"Thibault S."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"Thibault S."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"Meininger D."xsd:string
http://purl.uniprot.org/citations/23602659http://purl.uniprot.org/core/author"Meininger D."xsd:string