View source for 7yiy


==Cryo-EM structure of SPT-ORMDL3 complex==
<StructureSection load='7yiy' size='340' side='right'caption='[[7yiy]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7yiy]] is a 5 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=7YIY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YIY FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</scene>, <scene name='pdbligand=Z1T:N-[(2S,3R)-1,3-bis(oxidanyl)octadec-4-en-2-yl]tetracosanamide'>Z1T</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=7yiy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yiy OCA], [https://pdbe.org/7yiy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yiy RCSB], [https://www.ebi.ac.uk/pdbsum/7yiy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yiy ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/SPTC1_HUMAN SPTC1_HUMAN] Hereditary sensory and autonomic neuropathy type 1;Juvenile amyotrophic lateral sclerosis. The disease is caused by variants affecting the gene represented in this entry. Variants associated with ALS27 tend to disrupt the normal homeostatic regulation of serine palmitoyltransferase (SPT) by ORMDL proteins, resulting in up-regulated SPT activity and elevated levels of canonical SPT products.<ref>PMID:34059824</ref>   The disease is caused by variants affecting the gene represented in this entry. Variants associated with HSAN1A tend to increase serine palmitoyltransferase (SPT) usage of alanine or glycine rather than serine, resulting in deoxysphingolipid synthesis. Deoxysphingolipids cannot be efficiently degraded by the cell machinery and cause cell toxicity.<ref>PMID:34059824</ref> 
== Function ==
[https://www.uniprot.org/uniprot/SPTC1_HUMAN SPTC1_HUMAN] Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases. The SPT complex is also composed of SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer with SPTLC2 or SPTLC3 forms the catalytic core (PubMed:19416851, PubMed:33558762, PubMed:36170811). The composition of the serine palmitoyltransferase (SPT) complex determines the substrate preference (PubMed:19416851, PubMed:33558762). The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA (PubMed:19416851, PubMed:19648650). The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference (PubMed:19416851, PubMed:19648650, PubMed:33558761, PubMed:33558762). Required for adipocyte cell viability and metabolic homeostasis (By similarity).[UniProtKB:O35704]<ref>PMID:19416851</ref> <ref>PMID:19648650</ref> <ref>PMID:33558761</ref> <ref>PMID:33558762</ref> <ref>PMID:36170811</ref> 

==See Also==
*[[Serine palmitoyltransferase 3D structures|Serine palmitoyltransferase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gong X]]
[[Category: Liu P]]
[[Category: Xie T]]