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| | ==Crystal structure of E. coli FabI bound to the carbamoylated benzodiazaborine inhibitor 14b.== | | ==Crystal structure of E. coli FabI bound to the carbamoylated benzodiazaborine inhibitor 14b.== |
| - | <StructureSection load='5cg1' size='340' side='right' caption='[[5cg1]], [[Resolution|resolution]] 2.07Å' scene=''> | + | <StructureSection load='5cg1' size='340' side='right'caption='[[5cg1]], [[Resolution|resolution]] 2.07Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5cg1]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5CG1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5CG1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5cg1]] 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=5CG1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5CG1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BBN:1-HYDROXY-2,3,1-BENZODIAZABORININE-2(1H)-CARBOXAMIDE'>BBN</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</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]] 2.07Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5cfz|5cfz]], [[5cg2|5cg2]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BBN:1-HYDROXY-2,3,1-BENZODIAZABORININE-2(1H)-CARBOXAMIDE'>BBN</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene></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>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5cg1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cg1 OCA], [https://pdbe.org/5cg1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5cg1 RCSB], [https://www.ebi.ac.uk/pdbsum/5cg1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5cg1 ProSAT]</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=5cg1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5cg1 OCA], [http://pdbe.org/5cg1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5cg1 RCSB], [http://www.ebi.ac.uk/pdbsum/5cg1 PDBsum]</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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| | </div> | | </div> |
| | <div class="pdbe-citations 5cg1" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5cg1" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Enoyl-Acyl-Carrier Protein Reductase 3D structures|Enoyl-Acyl-Carrier Protein Reductase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Jordan, C A]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Vey, J L]]
| + | [[Category: Large Structures]] |
| - | [[Category: Antibiotic]]
| + | [[Category: Jordan CA]] |
| - | [[Category: Enoyl-acp reductase]]
| + | [[Category: Vey JL]] |
| - | [[Category: Nad]] | + | |
| - | [[Category: Oxidoreducatase-oxidoreducatase inhibitor complex]] | + | |
| - | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | + | |
| 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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