3VZB

Crystal structure of Sphingosine Kinase 1

Summary for 3VZB

• Entry DOI: 10.2210/pdb3vzb/pdb
• Related: 3VZC 3VZD
• Descriptor: Sphingosine kinase 1, (2S,3R,4E)-2-aminooctadec-4-ene-1,3-diol, SULFATE ION, ... (5 entities in total)
• Functional Keywords: lipid kinase, transferase-inhibitor complex, transferase/inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q9NYA1
• Total number of polymer chains: 3
• Total formula weight: 121399.46

Authors

Min, X.,Walker, N.P.,Wang, Z. (deposition date: 2012-10-10, release date: 2013-05-08, Last modification date: 2024-05-29)

Primary citation

Wang, Z.,Min, X.,Xiao, S.H.,Johnstone, S.,Romanow, W.,Meininger, D.,Xu, H.,Liu, J.,Dai, J.,An, S.,Thibault, S.,Walker, N.
Molecular basis of sphingosine kinase 1 substrate recognition and catalysis.
Structure, 21:798-809, 2013

PubMed Abstract: 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.

PubMed: 23602659
DOI: 10.1016/j.str.2013.02.025

Experimental method

X-RAY DIFFRACTION (2 Å)