Sphingosine kinase
From Proteopedia
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The '''Sphingosine Kinase Type 1 (SphK1)''' structure reveals a two domain '''alpha-beta''' architecture. <ref name="wang">PMID:23602659</ref> The '''catalytic site''' (used in converting sphingosine to S1P-see below in "function" section for more details) is in a '''hydrophobic''' cleft, located between the two domains. <ref name="wang">PMID:23602659</ref> This hydrophobic cleft is an '''ideal binding pocket''' for a '''hydrophobic lipid''', like '''sphingosine''' (an '''18-carbon''' amino alcohol with an '''unsaturated''' '''hydrocarbon''' chain). <ref name="wang">PMID:23602659</ref> | The '''Sphingosine Kinase Type 1 (SphK1)''' structure reveals a two domain '''alpha-beta''' architecture. <ref name="wang">PMID:23602659</ref> The '''catalytic site''' (used in converting sphingosine to S1P-see below in "function" section for more details) is in a '''hydrophobic''' cleft, located between the two domains. <ref name="wang">PMID:23602659</ref> This hydrophobic cleft is an '''ideal binding pocket''' for a '''hydrophobic lipid''', like '''sphingosine''' (an '''18-carbon''' amino alcohol with an '''unsaturated''' '''hydrocarbon''' chain). <ref name="wang">PMID:23602659</ref> | ||
| - | <table><tr><td | + | <table><tr><td colspan='2'>[[3vzb]] is a 3 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=3VZB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3VZB FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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">[[3vzc|3vzc]], [[3vzd|3vzd]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3vzc|3vzc]], [[3vzd|3vzd]]</td></tr> | ||
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<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=3vzb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vzb OCA], [http://pdbe.org/3vzb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vzb RCSB], [http://www.ebi.ac.uk/pdbsum/3vzb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vzb ProSAT]</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=3vzb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3vzb OCA], [http://pdbe.org/3vzb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3vzb RCSB], [http://www.ebi.ac.uk/pdbsum/3vzb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3vzb ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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== Function == | == Function == | ||
'''Sphingolipids''' are a class of lipids, containing a sphingosine base moiety, essential for eukaryotic cell membrane structure and function. <ref name="futerman">PMID:15289826</ref> Importantly, sphingolipids can additionally act as critical signaling molecules used in many eukaryotic homeostatic cellular processes, such as inflammation, proliferation, apoptosis, cell migration, and '''pathogen defense'''. <ref name="futerman">PMID:15289826</ref> Because of this, it is critical for sphingolipids and their metabolizing enzymes to exist in a delicate homeostatic balance within the eukaryotic cell system. | '''Sphingolipids''' are a class of lipids, containing a sphingosine base moiety, essential for eukaryotic cell membrane structure and function. <ref name="futerman">PMID:15289826</ref> Importantly, sphingolipids can additionally act as critical signaling molecules used in many eukaryotic homeostatic cellular processes, such as inflammation, proliferation, apoptosis, cell migration, and '''pathogen defense'''. <ref name="futerman">PMID:15289826</ref> Because of this, it is critical for sphingolipids and their metabolizing enzymes to exist in a delicate homeostatic balance within the eukaryotic cell system. | ||
Revision as of 19:05, 25 April 2022
Structure
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References
- ↑ 1.0 1.1 1.2 1.3 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
- ↑ 2.0 2.1 2.2 Futerman AH, Hannun YA. The complex life of simple sphingolipids. EMBO Rep. 2004 Aug;5(8):777-82. doi: 10.1038/sj.embor.7400208. PMID:15289826 doi:http://dx.doi.org/10.1038/sj.embor.7400208
- ↑ 3.0 3.1 3.2 3.3 3.4 Spiegel S, Milstien S. Sphingosine-1-phosphate: an enigmatic signalling lipid. Nat Rev Mol Cell Biol. 2003 May;4(5):397-407. doi: 10.1038/nrm1103. PMID:12728273 doi:http://dx.doi.org/10.1038/nrm1103
