3vzd: Difference between revisions
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==Crystal structure of Sphingosine Kinase 1 with inhibitor and ADP== | |||
<StructureSection load='3vzd' size='340' side='right' caption='[[3vzd]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
{ | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3vzd]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3VZD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VZD FirstGlance]. <br> | |||
==Function== | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=POP:PYROPHOSPHATE+2-'>POP</scene>, <scene name='pdbligand=UUL:4-{[4-(4-CHLOROPHENYL)-1,3-THIAZOL-2-YL]AMINO}PHENOL'>UUL</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3vzb|3vzb]], [[3vzc|3vzc]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SPHK1, SPHK, SPK ([http://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'>[http://en.wikipedia.org/wiki/Sphinganine_kinase Sphinganine kinase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3vzd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vzd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3vzd RCSB], [http://www.ebi.ac.uk/pdbsum/3vzd PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://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> | [[http://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> | ||
<div style="background-color:#fffaf0;"> | |||
== 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Sphinganine kinase]] | [[Category: Sphinganine kinase]] | ||
[[Category: Min, X | [[Category: Min, X]] | ||
[[Category: Walker, N P | [[Category: Walker, N P]] | ||
[[Category: Wang, Z | [[Category: Wang, Z]] | ||
[[Category: Lipid kinase]] | [[Category: Lipid kinase]] | ||
[[Category: Transferase-inhibitor complex]] | [[Category: Transferase-inhibitor complex]] | ||
