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3vzb

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Revision as of 04:56, 25 August 2022

Crystal structure of Sphingosine Kinase 1

Structural highlights

3vzb is a 3 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	3vzc, 3vzd
Activity:	Sphinganine kinase, with EC number 2.7.1.91
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Alvarez SE, Harikumar KB, Hait NC, Allegood J, Strub GM, Kim EY, Maceyka M, Jiang H, Luo C, Kordula T, Milstien S, Spiegel S. Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2. Nature. 2010 Jun 24;465(7301):1084-8. doi: 10.1038/nature09128. PMID:20577214 doi:10.1038/nature09128
↑ Wang Z, Min X, Xiao SH, 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. 2013 Apr 16. pii: S0969-2126(13)00086-5. doi:, 10.1016/j.str.2013.02.025. PMID:23602659 doi:http://dx.doi.org/10.1016/j.str.2013.02.025

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3vzb"

@@ Line 3: / Line 3: @@
 <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/Human Human]. 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>
+<table><tr><td colspan='2'>[[3vzb]] is a 3 chain structure. 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='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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3vzc|3vzc]], [[3vzd|3vzd]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SPHK1, SPHK, SPK ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Sphinganine_kinase Sphinganine kinase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.91 2.7.1.91] </span></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>
@@ Line 25: / Line 24: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Sphinganine kinase]]

3vzb

From Proteopedia

Revision as of 04:56, 25 August 2022

Crystal structure of Sphingosine Kinase 1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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