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4bmk

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{{STRUCTURE_4bmk| PDB=4bmk | SCENE= }}
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==Serine Palmitoyltransferase K265A from S. paucimobilis with bound PLP- Myriocin Aldimine==
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===Serine Palmitoyltransferase K265A from S. paucimobilis with bound PLP- Myriocin Aldimine===
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<StructureSection load='4bmk' size='340' side='right' caption='[[4bmk]], [[Resolution|resolution]] 1.62&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23957439}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4BMK FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Serine_C-palmitoyltransferase Serine C-palmitoyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.50 2.3.1.50] </span></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=4bmk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4bmk OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4bmk RCSB], [http://www.ebi.ac.uk/pdbsum/4bmk PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==About this Structure==
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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>
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[[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].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<ref group="xtra">PMID:023957439</ref><references group="xtra"/><references/>
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</div>
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==See Also==
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*[[Serine palmitoyltransferase|Serine palmitoyltransferase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Serine C-palmitoyltransferase]]
[[Category: Serine C-palmitoyltransferase]]
[[Category: Sphingomonas paucimobilis]]
[[Category: Sphingomonas paucimobilis]]
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[[Category: Beattie, A E.]]
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[[Category: Beattie, A E]]
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[[Category: Campopiano, D J.]]
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[[Category: Campopiano, D J]]
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[[Category: Clarke, D J.]]
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[[Category: Clarke, D J]]
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[[Category: Dunn, T M.]]
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[[Category: Dunn, T M]]
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[[Category: Lowther, J.]]
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[[Category: Lowther, J]]
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[[Category: McMahon, S A.]]
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[[Category: McMahon, S A]]
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[[Category: Naismith, J H.]]
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[[Category: Naismith, J H]]
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[[Category: Wadsworth, J M.]]
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[[Category: Wadsworth, J M]]
[[Category: Antibiotic isp-1]]
[[Category: Antibiotic isp-1]]
[[Category: External aldimine]]
[[Category: External aldimine]]

Revision as of 09:59, 21 December 2014

Serine Palmitoyltransferase K265A from S. paucimobilis with bound PLP- Myriocin Aldimine

4bmk, resolution 1.62Å

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