View source for 4ls5


==Crystal structure of beta-ketoacyl-ACP synthase II (FabF) from Bacillus subtilis==
<StructureSection load='4ls5' size='340' side='right'caption='[[4ls5]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4ls5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis_subsp._subtilis_str._168 Bacillus subtilis subsp. subtilis str. 168]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LS5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LS5 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]] 1.803&#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=K:POTASSIUM+ION'>K</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=4ls5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ls5 OCA], [https://pdbe.org/4ls5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ls5 RCSB], [https://www.ebi.ac.uk/pdbsum/4ls5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ls5 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FABF_BACSU FABF_BACSU] Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cerulenin is a fungal toxin that inhibits both eukaryotic and prokaryotic ketoacyl-ACP synthases or condensing enzymes. It has been used experimentally to treat cancer, obesity and is a potent inhibitor of bacterial growth. Understanding the molecular mechanisms of resistance to cerulenin and similar compounds is thus highly relevant for human health. We had previously described a Bacillus subtilis cerulenin-resistant strain, expressing a point-mutated condensing enzyme FabF (FabF[I108F]). We now report the crystal structures of wild type FabF (wtFabF) from B. subtilis, both alone and in complex with cerulenin, as well as of the FabF[I108F] mutant protein. The 3D structure of FabF[I108F] constitutes the first atomic model of a condensing enzyme that remains active in the presence of the inhibitor. Soaking the mycotoxin into preformed wtFabF crystals, allowed for non-covalent binding into its specific pocket within the FabF core. But, most interestingly, only co-crystallization experiments allowed us to trap the covalent complex. Our structure shows that the covalent bond between Cys163 and cerulenin, in contrast to what was previously proposed, implicates carbon C3 of the inhibitor. The similarities between Escherichia coli and B. subtilis FabF structures did not explain the reported inability of ecFabF[I108F] to elongate medium and long-chain acyl-ACPs. We now demonstrate that the E. coli modified enzyme efficiently catalyzes the synthesis of medium and long-chain ketoacyl-ACPs. We also characterized another cerulenin-insensitive form of FabF, conferring a different phenotype in B. subtilis. The structural, biochemical and physiological data presented, shed light on the mechanisms of FabF catalysis and resistance to cerulenin. This article is protected by copyright. All rights reserved. STRUCTURED DIGITAL ABSTRACT: FabF and FabF bind by x-ray crystallography (View interaction).

Structural insights into bacterial resistance to cerulenin.,Trajtenberg F, Altabe S, Larrieux N, Ficarra F, de Mendoza D, Buschiazzo A, Schujman GE FEBS J. 2014 Mar 19. doi: 10.1111/febs.12785. PMID:24641521<ref>PMID:24641521</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ls5" style="background-color:#fffaf0;"></div>

==See Also==
*[[Acyl carrier protein synthase 3D structures|Acyl carrier protein synthase 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Bacillus subtilis subsp. subtilis str. 168]]
[[Category: Large Structures]]
[[Category: Buschiazzo A]]
[[Category: Larrieux N]]
[[Category: Trajtenberg F]]