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| | ==Crystal Structure of Porphyromonas gingivalis Enoyl-ACP Reductase II (FabK) with cofactors NADPH and FMN== | | ==Crystal Structure of Porphyromonas gingivalis Enoyl-ACP Reductase II (FabK) with cofactors NADPH and FMN== |
| - | <StructureSection load='4iql' size='340' side='right' caption='[[4iql]], [[Resolution|resolution]] 1.94Å' scene=''> | + | <StructureSection load='4iql' size='340' side='right'caption='[[4iql]], [[Resolution|resolution]] 1.94Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4iql]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Porgi Porgi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IQL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IQL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4iql]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Porphyromonas_gingivalis_W83 Porphyromonas gingivalis W83]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IQL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IQL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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]] 1.938Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=FMN:FLAVIN+MONONUCLEOTIDE'>FMN</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fabK, PG_1416 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=242619 PORGI])</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=4iql FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iql OCA], [https://pdbe.org/4iql PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iql RCSB], [https://www.ebi.ac.uk/pdbsum/4iql PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iql 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> | + | |
| - | <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=4iql FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iql OCA], [http://pdbe.org/4iql PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4iql RCSB], [http://www.ebi.ac.uk/pdbsum/4iql PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4iql ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q7MAW0_PORGI Q7MAW0_PORGI] |
| | <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== |
| - | *[[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: Porgi]] | + | [[Category: Large Structures]] |
| - | [[Category: Boci, T]] | + | [[Category: Porphyromonas gingivalis W83]] |
| - | [[Category: Hevener, K E]] | + | [[Category: Boci T]] |
| - | [[Category: Johnson, M E]] | + | [[Category: Hevener KE]] |
| - | [[Category: Mehboob, S]] | + | [[Category: Johnson ME]] |
| - | [[Category: Santarsiero, B D]] | + | [[Category: Mehboob S]] |
| - | [[Category: Su, P C]] | + | [[Category: Santarsiero BD]] |
| - | [[Category: Truong, K]] | + | [[Category: Su P-C]] |
| - | [[Category: Fatty acid binding]]
| + | [[Category: Truong K]] |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Reduction]]
| + | |
| - | [[Category: Tim barrel]]
| + | |
| Structural highlights
4iql is a 2 chain structure with sequence from Porphyromonas gingivalis W83. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.938Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
Q7MAW0_PORGI
Publication Abstract from PubMed
Enoyl-acyl carrier protein (ACP) reductase II (FabK) is a critical rate-limiting enzyme in the bacterial type II fatty-acid synthesis (FAS II) pathway. FAS II pathway enzymes are markedly disparate from their mammalian analogs in the FAS I pathway in both structure and mechanism. Enzymes involved in bacterial fatty-acid synthesis represent viable drug targets for Gram-negative pathogens, and historical precedent exists for targeting them in the treatment of diseases of the oral cavity. The Gram-negative organism Porphyromonas gingivalis represents a key causative agent of the costly and highly prevalent disease known as chronic periodontitis, and exclusively expresses FabK as its enoyl reductase enzyme in the FAS-II pathway. Together, these characteristics distinguish P. gingivalis FabK (PgFabK) as an attractive and novel narrow-spectrum antibacterial target candidate. PgFabK is a flavoenzyme that is dependent on FMN and NADPH as cofactors for the enzymatic reaction, which reduces the enoyl substrate via a ping-pong mechanism. Here, the structure of the PgFabK enzyme as determined using X-ray crystallography is reported to 1.9 A resolution with endogenous FMN fully resolved and the NADPH cofactor partially resolved. PgFabK possesses a TIM-barrel motif, and all flexible loops are visible. The determined structure has allowed insight into the structural basis for the NADPH dependence observed in PgFabK and the role of a monovalent cation that has been observed in previous studies to be stringently required for FabK activity. The PgFabK structure and the insights gleaned from its analysis will facilitate structure-based drug-discovery efforts towards the prevention and treatment of P. gingivalis infection.
Structural characterization of Porphyromonas gingivalis enoyl-ACP reductase II (FabK).,Hevener KE, Santarsiero BD, Lee H, Jones JA, Boci T, Johnson ME, Mehboob S Acta Crystallogr F Struct Biol Commun. 2018 Feb 1;74(Pt 2):105-112. doi:, 10.1107/S2053230X18000262. Epub 2018 Jan 26. PMID:29400320[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Hevener KE, Santarsiero BD, Lee H, Jones JA, Boci T, Johnson ME, Mehboob S. Structural characterization of Porphyromonas gingivalis enoyl-ACP reductase II (FabK). Acta Crystallogr F Struct Biol Commun. 2018 Feb 1;74(Pt 2):105-112. doi:, 10.1107/S2053230X18000262. Epub 2018 Jan 26. PMID:29400320 doi:http://dx.doi.org/10.1107/S2053230X18000262
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