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| | ==Structure of ENR G93V mutant-NAD+-triclosan complex== | | ==Structure of ENR G93V mutant-NAD+-triclosan complex== |
| - | <StructureSection load='3pjf' size='340' side='right' caption='[[3pjf]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='3pjf' size='340' side='right'caption='[[3pjf]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3pjf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PJF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PJF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3pjf]] 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=3PJF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PJF FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=TCL:TRICLOSAN'>TCL</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]] 1.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3pjd|3pjd]], [[3pje|3pje]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=TCL:TRICLOSAN'>TCL</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ENVM, fabI ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli])</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=3pjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pjf OCA], [https://pdbe.org/3pjf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pjf RCSB], [https://www.ebi.ac.uk/pdbsum/3pjf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pjf 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=3pjf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pjf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3pjf RCSB], [http://www.ebi.ac.uk/pdbsum/3pjf 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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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3pjf" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Enoyl-Acyl-Carrier Protein Reductase|Enoyl-Acyl-Carrier Protein Reductase]] | + | *[[Enoyl-Acyl-Carrier Protein Reductase 3D structures|Enoyl-Acyl-Carrier Protein Reductase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Escherichia coli]] | + | [[Category: Escherichia coli K-12]] |
| - | [[Category: Chang, H J]] | + | [[Category: Large Structures]] |
| - | [[Category: Kim, H T]] | + | [[Category: Chang HJ]] |
| - | [[Category: Shin, D G]] | + | [[Category: Kim HT]] |
| - | [[Category: Antibiotic resistance]] | + | [[Category: Shin DG]] |
| - | [[Category: Fatty acid biosynthesis]]
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| - | [[Category: Inner membrane]]
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| - | [[Category: Lipid synthesis]]
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| - | [[Category: Membrane]]
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| - | [[Category: Nad]]
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| - | [[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
Triclosan (5-chloro-2-(2,4-dichloro-phenoxy)-phenol, TCL) is a well known inhibitor against enoyl-acyl carrier protein reductase (ENR), an enzyme critical for cell-wall synthesis of bacteria. The inhibitory concentration at 50% inhibition (IC(50)) of TCL against the Escherichia coli ENR is 150nM for wild type (WT), 380, 470 and 68,500nM for Ala, Ser and Val mutants, respectively. To understand this high TCL resistance in the G93V mutant, we obtained the crystal structures of mutated ENRs complexed with TCL and NAD(+). The X-ray structural analysis along with the ab initio calculations and molecular dynamics simulations explains the serious consequence in the G93V mutant complex. The major interactions around TCL due to the aromatic(cation)-aromatic and hydrogen bonding interactions are found to be conserved both in WT and mutant complexes. Thus, the overall structural change of protein is minimal except that a flexible alpha-helical turn around TCL is slightly pushed away due to the presence of the bulky valine group. However, TCL shows substantial edge-to-face aromatic (pi)-interactions with both the flexible R192-F203 region and the residues in the close vicinity of G93. The weakening of some edge-to-face aromatic interactions around TCL in the G93V mutant results in serious resistance to TCL. This understanding is beneficial to design new generation of antibiotics which will effectively act on the mutant ENRs.
Structural basis of triclosan resistance.,Jiten Singh N, Shin D, Lee HM, Kim HT, Chang HJ, Cho JM, Kim KS, Ro S J Struct Biol. 2011 Apr;174(1):173-9. Epub 2010 Nov 19. PMID:21094257[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
- ↑ Jiten Singh N, Shin D, Lee HM, Kim HT, Chang HJ, Cho JM, Kim KS, Ro S. Structural basis of triclosan resistance. J Struct Biol. 2011 Apr;174(1):173-9. Epub 2010 Nov 19. PMID:21094257 doi:10.1016/j.jsb.2010.11.008
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