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{{STRUCTURE_4bmk|  PDB=4bmk  |  SCENE=  }}
===Serine Palmitoyltransferase K265A from S. paucimobilis with bound PLP- Myriocin Aldimine===
{{ABSTRACT_PUBMED_23957439}}


==About this Structure==
==Serine Palmitoyltransferase K265A from S. paucimobilis with bound PLP- Myriocin Aldimine==
[[4bmk]] is a 2 chain structure with sequence from [http://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].  
<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.


==Reference==
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>
<ref group="xtra">PMID:023957439</ref><references group="xtra"/><references/>
 
[[Category: Serine C-palmitoyltransferase]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<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: Sphingomonas paucimobilis]]
[[Category: Beattie, A E.]]
[[Category: Beattie AE]]
[[Category: Campopiano, D J.]]
[[Category: Campopiano DJ]]
[[Category: Clarke, D J.]]
[[Category: Clarke DJ]]
[[Category: Dunn, T M.]]
[[Category: Dunn TM]]
[[Category: Lowther, J.]]
[[Category: Lowther J]]
[[Category: McMahon, S A.]]
[[Category: McMahon SA]]
[[Category: Naismith, J H.]]
[[Category: Naismith JH]]
[[Category: Wadsworth, J M.]]
[[Category: Wadsworth JM]]
[[Category: Antibiotic isp-1]]
[[Category: External aldimine]]
[[Category: Inhibitor]]
[[Category: Natural product]]
[[Category: Sphingolipid]]
[[Category: Transferase]]
[[Category: Transferase-antibiotic complex]]
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