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| | <StructureSection load='6d3q' size='340' side='right'caption='[[6d3q]], [[Resolution|resolution]] 2.24Å' scene=''> | | <StructureSection load='6d3q' size='340' side='right'caption='[[6d3q]], [[Resolution|resolution]] 2.24Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6d3q]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D3Q OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D3Q FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6d3q]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D3Q OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D3Q FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4NG:[(3S,5S)-1,5-DIHYDROXY-2-OXOPYRROLIDIN-3-YL]PHOSPHONIC+ACID'>4NG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.24Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">eno ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4NG:[(3S,5S)-1,5-DIHYDROXY-2-OXOPYRROLIDIN-3-YL]PHOSPHONIC+ACID'>4NG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphopyruvate_hydratase Phosphopyruvate hydratase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.2.1.11 4.2.1.11] </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=6d3q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d3q OCA], [https://pdbe.org/6d3q PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d3q RCSB], [https://www.ebi.ac.uk/pdbsum/6d3q PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d3q 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=6d3q FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d3q OCA], [http://pdbe.org/6d3q PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d3q RCSB], [http://www.ebi.ac.uk/pdbsum/6d3q PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d3q ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ENO_ECO45 ENO_ECO45]] Catalyzes the reversible conversion of 2-phosphoglycerate into phosphoenolpyruvate. It is essential for the degradation of carbohydrates via glycolysis. | + | [https://www.uniprot.org/uniprot/ENO_ECOLI ENO_ECOLI] Catalyzes the reversible conversion of 2-phosphoglycerate into phosphoenolpyruvate. It is essential for the degradation of carbohydrates via glycolysis. It is also a component of the RNA degradosome, a multi-enzyme complex involved in RNA processing and messenger RNA degradation. Its interaction with RNase E is important for the turnover of mRNA, in particular on transcripts encoding enzymes of energy-generating metabolic routes. Its presence in the degradosome is required for the response to excess phosphosugar. May play a regulatory role in the degradation of specific RNAs, such as ptsG mRNA, therefore linking cellular metabolic status with post-translational gene regulation.<ref>PMID:8610017</ref> <ref>PMID:14981237</ref> <ref>PMID:15522087</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 6d3q" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6d3q" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Enolase 3D structures|Enolase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus coli migula 1895]] | + | [[Category: Escherichia coli]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Phosphopyruvate hydratase]]
| + | [[Category: Erlandsen H]] |
| - | [[Category: Erlandsen, H]] | + | [[Category: Hazeen A]] |
| - | [[Category: Hazeen, A]] | + | [[Category: Krucinska J]] |
| - | [[Category: Krucinska, J]] | + | [[Category: Wright D]] |
| - | [[Category: Wright, D]] | + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Enolase]]
| + | |
| - | [[Category: Lyase]]
| + | |
| - | [[Category: Lyase-lyase inhibitor complex]]
| + | |
| - | [[Category: Natural inhibitor]]
| + | |
| - | [[Category: Sf2312]]
| + | |
| Structural highlights
Function
ENO_ECOLI Catalyzes the reversible conversion of 2-phosphoglycerate into phosphoenolpyruvate. It is essential for the degradation of carbohydrates via glycolysis. It is also a component of the RNA degradosome, a multi-enzyme complex involved in RNA processing and messenger RNA degradation. Its interaction with RNase E is important for the turnover of mRNA, in particular on transcripts encoding enzymes of energy-generating metabolic routes. Its presence in the degradosome is required for the response to excess phosphosugar. May play a regulatory role in the degradation of specific RNAs, such as ptsG mRNA, therefore linking cellular metabolic status with post-translational gene regulation.[1] [2] [3]
Publication Abstract from PubMed
Many years ago, the natural secondary metabolite SF2312, produced by the actinomycete Micromonospora, was reported to display broad spectrum antibacterial properties against both Gram-positive and Gram-negative bacteria. Recent studies have revealed that SF2312, a natural phosphonic acid, functions as a potent inhibitor of human enolase. The mechanism of SF2312 inhibition of bacterial enolase and its role in bacterial growth and reproduction, however, have remained elusive. In this work, we detail a structural analysis of E. coli enolase bound to both SF2312 and its oxidized imide-form. Our studies support a model in which SF2312 acts as an analog of a high energy intermediate formed during the catalytic process. Biochemical, biophysical, computational and kinetic characterization of these compounds confirm that altering features characteristic of a putative carbanion (enolate) intermediate significantly reduces the potency of enzyme inhibition. When SF2312 is combined with fosfomycin in the presence of glucose-6 phosphate, significant synergy is observed. This suggests the two agents could be used as a potent combination, targeting distinct cellular mechanism for the treatment of bacterial infections. Together, our studies rationalize the structure-activity relationships for these phosphonates and validate enolase as a promising target for antibiotic discovery.
Functional and structural basis of E. coli enolase inhibition by SF2312: a mimic of the carbanion intermediate.,Krucinska J, Lombardo MN, Erlandsen H, Hazeen A, Duay SS, Pattis JG, Robinson VL, May ER, Wright DL Sci Rep. 2019 Nov 19;9(1):17106. doi: 10.1038/s41598-019-53301-3. PMID:31745118[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Py B, Higgins CF, Krisch HM, Carpousis AJ. A DEAD-box RNA helicase in the Escherichia coli RNA degradosome. Nature. 1996 May 9;381(6578):169-72. PMID:8610017 doi:http://dx.doi.org/10.1038/381169a0
- ↑ Bernstein JA, Lin PH, Cohen SN, Lin-Chao S. Global analysis of Escherichia coli RNA degradosome function using DNA microarrays. Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2758-63. Epub 2004 Feb 23. PMID:14981237 doi:http://dx.doi.org/10.1073/pnas.0308747101
- ↑ Morita T, Kawamoto H, Mizota T, Inada T, Aiba H. Enolase in the RNA degradosome plays a crucial role in the rapid decay of glucose transporter mRNA in the response to phosphosugar stress in Escherichia coli. Mol Microbiol. 2004 Nov;54(4):1063-75. PMID:15522087 doi:http://dx.doi.org/10.1111/j.1365-2958.2004.04329.x
- ↑ Krucinska J, Lombardo MN, Erlandsen H, Hazeen A, Duay SS, Pattis JG, Robinson VL, May ER, Wright DL. Functional and structural basis of E. coli enolase inhibition by SF2312: a mimic of the carbanion intermediate. Sci Rep. 2019 Nov 19;9(1):17106. doi: 10.1038/s41598-019-53301-3. PMID:31745118 doi:http://dx.doi.org/10.1038/s41598-019-53301-3
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