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| | ==Crystal structure of beta-ketoacyl-ACP synthase II (FabF) I108F mutant from Bacillus subtilis== | | ==Crystal structure of beta-ketoacyl-ACP synthase II (FabF) I108F mutant from Bacillus subtilis== |
| - | <StructureSection load='4ls6' size='340' side='right' caption='[[4ls6]], [[Resolution|resolution]] 1.56Å' scene=''> | + | <StructureSection load='4ls6' size='340' side='right'caption='[[4ls6]], [[Resolution|resolution]] 1.56Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ls6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Bacsu Bacsu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LS6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LS6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ls6]] 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=4LS6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LS6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ls5|4ls5]], [[4ls7|4ls7]], [[4ls8|4ls8]]</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=4ls6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ls6 OCA], [https://pdbe.org/4ls6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ls6 RCSB], [https://www.ebi.ac.uk/pdbsum/4ls6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ls6 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fabF, yjaY, BSU11340 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=224308 BACSU])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-ketoacyl-[acyl-carrier-protein]_synthase_II Beta-ketoacyl-[acyl-carrier-protein] synthase II], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.179 2.3.1.179] </span></td></tr>
| + | |
| - | <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=4ls6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ls6 OCA], [http://pdbe.org/4ls6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ls6 RCSB], [http://www.ebi.ac.uk/pdbsum/4ls6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ls6 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Acyl carrier protein synthase|Acyl carrier protein synthase]] | + | *[[Acyl carrier protein synthase 3D structures|Acyl carrier protein synthase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacsu]] | + | [[Category: Bacillus subtilis subsp. subtilis str. 168]] |
| - | [[Category: Buschiazzo, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Larrieux, N]] | + | [[Category: Buschiazzo A]] |
| - | [[Category: Trajtenberg, F]] | + | [[Category: Larrieux N]] |
| - | [[Category: Cerulenin resistant]] | + | [[Category: Trajtenberg F]] |
| - | [[Category: Fatty acid elongation]]
| + | |
| - | [[Category: Kasii]]
| + | |
| - | [[Category: Ketoacyl synthase]]
| + | |
| - | [[Category: Transferase]]
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| Structural highlights
Function
FABF_BACSU Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Trajtenberg F, Altabe S, Larrieux N, Ficarra F, de Mendoza D, Buschiazzo A, Schujman GE. Structural insights into bacterial resistance to cerulenin. FEBS J. 2014 Mar 19. doi: 10.1111/febs.12785. PMID:24641521 doi:http://dx.doi.org/10.1111/febs.12785
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