View source for 3vzb


==Crystal structure of Sphingosine Kinase 1==
<StructureSection load='3vzb' size='340' side='right'caption='[[3vzb]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3vzb]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VZB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3VZB FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SQS:(2S,3R,4E)-2-AMINOOCTADEC-4-ENE-1,3-DIOL'>SQS</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3vzb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vzb OCA], [https://pdbe.org/3vzb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3vzb RCSB], [https://www.ebi.ac.uk/pdbsum/3vzb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3vzb ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SPHK1_HUMAN SPHK1_HUMAN] Catalyzes the phosphorylation of sphingosine to form sphingosine 1-phosphate (SPP), a lipid mediator with both intra- and extracellular functions. Also acts on D-erythro-sphingosine and to a lesser extent sphinganine, but not other lipids, such as D,L-threo-dihydrosphingosine, N,N-dimethylsphingosine, diacylglycerol, ceramide, or phosphatidylinositol.<ref>PMID:20577214</ref> 
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== Publication Abstract from PubMed ==
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 A 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.

Molecular Basis of Sphingosine Kinase 1 Substrate Recognition and Catalysis.,Wang Z, Min X, Xiao SH, Johnstone S, Romanow W, Meininger D, Xu H, Liu J, Dai J, An S, Thibault S, Walker N Structure. 2013 Apr 16. pii: S0969-2126(13)00086-5. doi:, 10.1016/j.str.2013.02.025. PMID:23602659<ref>PMID:23602659</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3vzb" style="background-color:#fffaf0;"></div>

==See Also==
*[[Sphingosine kinase|Sphingosine kinase]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Min X]]
[[Category: Walker NP]]
[[Category: Wang Z]]