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| | <StructureSection load='5cfz' size='340' side='right'caption='[[5cfz]], [[Resolution|resolution]] 1.97Å' scene=''> | | <StructureSection load='5cfz' size='340' side='right'caption='[[5cfz]], [[Resolution|resolution]] 1.97Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5cfz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CFZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CFZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5cfz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CFZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CFZ FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cg1|5cg1]], [[5cg2|5cg2]]</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]] 1.97Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fabI, envM, b1288, JW1281 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</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=5cfz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cfz OCA], [https://pdbe.org/5cfz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cfz RCSB], [https://www.ebi.ac.uk/pdbsum/5cfz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cfz ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Enoyl-[acyl-carrier-protein]_reductase_(NADH) Enoyl-[acyl-carrier-protein] reductase (NADH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.9 1.3.1.9] </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=5cfz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cfz OCA], [http://pdbe.org/5cfz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cfz RCSB], [http://www.ebi.ac.uk/pdbsum/5cfz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5cfz ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FABI_ECOLI FABI_ECOLI]] Catalyzes the reduction of a carbon-carbon double bond in an enoyl moiety that is covalently linked to an acyl carrier protein (ACP). Involved in the elongation cycle of fatty acid which are used in the lipid metabolism and in the biotin biosynthesis.<ref>PMID:8119879</ref> <ref>PMID:7592873</ref> <ref>PMID:20693992</ref> | + | [https://www.uniprot.org/uniprot/FABI_ECOLI FABI_ECOLI] Catalyzes the reduction of a carbon-carbon double bond in an enoyl moiety that is covalently linked to an acyl carrier protein (ACP). Involved in the elongation cycle of fatty acid which are used in the lipid metabolism and in the biotin biosynthesis.<ref>PMID:8119879</ref> <ref>PMID:7592873</ref> <ref>PMID:20693992</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Ecoli]] | + | [[Category: Escherichia coli K-12]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Jordan, C A]] | + | [[Category: Jordan CA]] |
| - | [[Category: Vey, J L]] | + | [[Category: Vey JL]] |
| - | [[Category: Antibiotic]]
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| - | [[Category: Enoyl-acp reductase]]
| + | |
| - | [[Category: Nad]]
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| - | [[Category: Oxidoreducatase]]
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| - | [[Category: Oxidoreductase]]
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| Structural highlights
Function
FABI_ECOLI Catalyzes the reduction of a carbon-carbon double bond in an enoyl moiety that is covalently linked to an acyl carrier protein (ACP). Involved in the elongation cycle of fatty acid which are used in the lipid metabolism and in the biotin biosynthesis.[1] [2] [3]
Publication Abstract from PubMed
Enoyl-ACP reductase, the last enzyme of the fatty-acid biosynthetic pathway, is the molecular target for several successful antibiotics such as the tuberculosis therapeutic isoniazid. It is currently under investigation as a narrow-spectrum antibiotic target for the treatment of several types of bacterial infections. The diazaborine family is a group of boron heterocycle-based synthetic antibacterial inhibitors known to target enoyl-ACP reductase. Development of this class of molecules has thus far focused solely on the sulfonyl-containing versions. Here, the requirement for the sulfonyl group in the diazaborine scaffold was investigated by examining several recently characterized enoyl-ACP reductase inhibitors that lack the sulfonyl group and exhibit additional variability in substitutions, size and flexibility. Biochemical studies are reported showing the inhibition of Escherichia coli enoyl-ACP reductase by four diazaborines, and the crystal structures of two of the inhibitors bound to E. coli enoyl-ACP reductase solved to 2.07 and 2.11 A resolution are reported. The results show that the sulfonyl group can be replaced with an amide or thioamide without disruption of the mode of inhibition of the molecule.
Crystallographic insights into the structure-activity relationships of diazaborine enoyl-ACP reductase inhibitors.,Jordan CA, Sandoval BA, Serobyan MV, Gilling DH, Groziak MP, Xu HH, Vey JL Acta Crystallogr F Struct Biol Commun. 2015 Dec 1;71(Pt 12):1521-30. doi:, 10.1107/S2053230X15022098. Epub 2015 Nov 27. PMID:26625295[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bergler H, Wallner P, Ebeling A, Leitinger B, Fuchsbichler S, Aschauer H, Kollenz G, Hogenauer G, Turnowsky F. Protein EnvM is the NADH-dependent enoyl-ACP reductase (FabI) of Escherichia coli. J Biol Chem. 1994 Feb 25;269(8):5493-6. PMID:8119879
- ↑ Heath RJ, Rock CO. Enoyl-acyl carrier protein reductase (fabI) plays a determinant role in completing cycles of fatty acid elongation in Escherichia coli. J Biol Chem. 1995 Nov 3;270(44):26538-42. PMID:7592873
- ↑ Lin S, Hanson RE, Cronan JE. Biotin synthesis begins by hijacking the fatty acid synthetic pathway. Nat Chem Biol. 2010 Sep;6(9):682-8. doi: 10.1038/nchembio.420. Epub 2010 Aug 8. PMID:20693992 doi:http://dx.doi.org/10.1038/nchembio.420
- ↑ Jordan CA, Sandoval BA, Serobyan MV, Gilling DH, Groziak MP, Xu HH, Vey JL. Crystallographic insights into the structure-activity relationships of diazaborine enoyl-ACP reductase inhibitors. Acta Crystallogr F Struct Biol Commun. 2015 Dec 1;71(Pt 12):1521-30. doi:, 10.1107/S2053230X15022098. Epub 2015 Nov 27. PMID:26625295 doi:http://dx.doi.org/10.1107/S2053230X15022098
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