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| | <StructureSection load='2ix4' size='340' side='right'caption='[[2ix4]], [[Resolution|resolution]] 1.95Å' scene=''> | | <StructureSection load='2ix4' size='340' side='right'caption='[[2ix4]], [[Resolution|resolution]] 1.95Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2ix4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Arath Arath]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IX4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IX4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2ix4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IX4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2IX4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6NA:HEXANOIC+ACID'>6NA</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1w0i|1w0i]], [[2iwy|2iwy]], [[2iwz|2iwz]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6NA:HEXANOIC+ACID'>6NA</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Beta-ketoacyl-[acyl-carrier-protein]_synthase_I Beta-ketoacyl-[acyl-carrier-protein] synthase I], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.41 2.3.1.41] </span></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=2ix4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ix4 OCA], [https://pdbe.org/2ix4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ix4 RCSB], [https://www.ebi.ac.uk/pdbsum/2ix4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ix4 ProSAT]</span></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=2ix4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ix4 OCA], [https://pdbe.org/2ix4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ix4 RCSB], [https://www.ebi.ac.uk/pdbsum/2ix4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ix4 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/KASM_ARATH KASM_ARATH]] Catalyzes all the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Able to elongate saturated acyl chains from 4 to at least 16 carbons. Uses malonyl-CoA but not acetyl-CoA as primer substrate. When expressed in a heterologous system, reveals a bimodal distribution of products, with peaks at C8 and C14-C16. The major product of the reaction (octanoyl-ACP) is required for the lipoylation of essential mitochondrial proteins.<ref>PMID:17616510</ref>
| + | [https://www.uniprot.org/uniprot/KASM_ARATH KASM_ARATH] Catalyzes all the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Able to elongate saturated acyl chains from 4 to at least 16 carbons. Uses malonyl-CoA but not acetyl-CoA as primer substrate. When expressed in a heterologous system, reveals a bimodal distribution of products, with peaks at C8 and C14-C16. The major product of the reaction (octanoyl-ACP) is required for the lipoylation of essential mitochondrial proteins.<ref>PMID:17616510</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Arath]] | + | [[Category: Arabidopsis thaliana]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Christensen, C E]] | + | [[Category: Christensen CE]] |
| - | [[Category: Henriksen, A]] | + | [[Category: Henriksen A]] |
| - | [[Category: Kragelund, B B]] | + | [[Category: Kragelund BB]] |
| - | [[Category: Wettstein-Knowles, P von]] | + | [[Category: Von Wettstein-Knowles P]] |
| - | [[Category: Acyl complex]]
| + | |
| - | [[Category: Acyltransferase]]
| + | |
| - | [[Category: Condensing enzyme]]
| + | |
| - | [[Category: Fatty acid biosynthesis]]
| + | |
| - | [[Category: Fatty acid elongation]]
| + | |
| - | [[Category: Lipid metabolism]]
| + | |
| - | [[Category: Lipid synthesis]]
| + | |
| - | [[Category: Mitochondrion]]
| + | |
| - | [[Category: Synthase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transit peptide]]
| + | |
| Structural highlights
Function
KASM_ARATH Catalyzes all the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Able to elongate saturated acyl chains from 4 to at least 16 carbons. Uses malonyl-CoA but not acetyl-CoA as primer substrate. When expressed in a heterologous system, reveals a bimodal distribution of products, with peaks at C8 and C14-C16. The major product of the reaction (octanoyl-ACP) is required for the lipoylation of essential mitochondrial proteins.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Two distinct ways of organizing fatty acid biosynthesis exist: the multifunctional type I fatty acid synthase (FAS) of mammals, fungi, and lower eukaryotes with activities residing on one or two polypeptides; and the dissociated type II FAS of prokaryotes, plastids, and mitochondria with individual activities encoded by discrete genes. The beta-ketoacyl [ACP] synthase (KAS) moiety of the mitochondrial FAS (mtKAS) is targeted by the antibiotic cerulenin and possibly by the other antibiotics inhibiting prokaryotic KASes: thiolactomycin, platensimycin, and the alpha-methylene butyrolactone, C75. The high degree of structural similarity between mitochondrial and prokaryotic KASes complicates development of novel antibiotics targeting prokaryotic KAS without affecting KAS domains of cytoplasmic FAS. KASes catalyze the C(2) fatty acid elongation reaction using either a Cys-His-His or Cys-His-Asn catalytic triad. Three KASes with different substrate specificities participate in synthesis of the C(16) and C(18) products of prokaryotic FAS. By comparison, mtKAS carries out all elongation reactions in the mitochondria. We present the X-ray crystal structures of the Cys-His-His-containing human mtKAS and its hexanoyl complex plus the hexanoyl complex of the plant mtKAS from Arabidopsis thaliana. The structures explain (1) the bimodal (C(6) and C(10)-C(12)) substrate preferences leading to the C(8) lipoic acid precursor and long chains for the membranes, respectively, and (2) the low cerulenin sensitivity of the human enzyme; and (3) reveal two different potential acyl-binding-pocket extensions. Rearrangements taking place in the active site, including subtle changes in the water network, indicate a change in cooperativity of the active-site histidines upon primer binding.
Structure of the human beta-ketoacyl [ACP] synthase from the mitochondrial type II fatty acid synthase.,Christensen CE, Kragelund BB, von Wettstein-Knowles P, Henriksen A Protein Sci. 2007 Feb;16(2):261-72. PMID:17242430[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ewald R, Kolukisaoglu U, Bauwe U, Mikkat S, Bauwe H. Mitochondrial protein lipoylation does not exclusively depend on the mtKAS pathway of de novo fatty acid synthesis in Arabidopsis. Plant Physiol. 2007 Sep;145(1):41-8. Epub 2007 Jul 6. PMID:17616510 doi:http://dx.doi.org/10.1104/pp.107.104000
- ↑ Christensen CE, Kragelund BB, von Wettstein-Knowles P, Henriksen A. Structure of the human beta-ketoacyl [ACP] synthase from the mitochondrial type II fatty acid synthase. Protein Sci. 2007 Feb;16(2):261-72. PMID:17242430 doi:http://dx.doi.org/16/2/261
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