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==Serine Palmitoyltransferase K265A from S. paucimobilis with bound PLP- Myriocin Aldimine==
<StructureSection load='4bmk' size='340' side='right'caption='[[4bmk]], [[Resolution|resolution]] 1.62&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4bmk]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Sphingomonas_paucimobilis Sphingomonas paucimobilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4BMK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4BMK 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]] 1.62&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MYB:DECARBOXYLATED+MYRIOCIN'>MYB</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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=4bmk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bmk OCA], [https://pdbe.org/4bmk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4bmk RCSB], [https://www.ebi.ac.uk/pdbsum/4bmk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4bmk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SPT_SPHPI SPT_SPHPI] Catalyzes the condensation of L-serine with palmitoyl-CoA (hexadecanoyl-CoA) to produce 3-oxosphinganine (PubMed:11279212, PubMed:17557831, PubMed:17559874, PubMed:19376777). Exhibits a broad substrate specificity concerning the chain length and the degree of unsaturation of acyl-CoA (PubMed:11279212, PubMed:19376777).<ref>PMID:11279212</ref> <ref>PMID:17557831</ref> <ref>PMID:17559874</ref> <ref>PMID:19376777</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Sphingolipids (SLs) are essential components of cellular membranes formed from the condensation of L-serine and a long-chain acyl thioester. This first step is catalysed by the pyridoxal 5-phosphate (PLP)-dependent enzyme serine palmitoyltransferase (SPT) which is a promising therapeutic target. The fungal natural product myriocin is a potent inhibitor of SPT and is widely-used to block SL biosynthesis despite a lack of a detailed understanding of its molecular mechanism. By combining spectroscopy, mass spectrometry, x-ray crystallography and kinetics we have characterised the molecular details of SPT inhibition by myriocin. Myriocin initially forms an external aldimine with PLP at the active site and a structure of the resulting co-complex explains its nanomolar affinity for the enzyme. This co-complex then catalytically degrades via an unexpected 'retro-aldol like' cleavage mechanism to a C18 aldehyde which in turn acts as a suicide inhibitor of SPT by covalent modification of the essential catalytic lysine. This surprising dual mechanism of inhibition rationalises the extraordinary potency and longevity of myriocin inhibition.

The chemical basis of serine palmitoyltransferase inhibition by myriocin.,Wadsworth JM, Clarke DJ, McMahon SA, Lowther JP, Beattie AE, Langridge-Smith PR, Broughton HB, Dunn TM, Naismith JH, Campopiano DJ J Am Chem Soc. 2013 Aug 19. PMID:23957439<ref>PMID:23957439</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 4bmk" style="background-color:#fffaf0;"></div>

==See Also==
*[[Serine palmitoyltransferase 3D structures|Serine palmitoyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Sphingomonas paucimobilis]]
[[Category: Beattie AE]]
[[Category: Campopiano DJ]]
[[Category: Clarke DJ]]
[[Category: Dunn TM]]
[[Category: Lowther J]]
[[Category: McMahon SA]]
[[Category: Naismith JH]]
[[Category: Wadsworth JM]]