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| | <StructureSection load='2o99' size='340' side='right'caption='[[2o99]], [[Resolution|resolution]] 1.70Å' scene=''> | | <StructureSection load='2o99' size='340' side='right'caption='[[2o99]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2o99]] is a 4 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=2O99 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2O99 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2o99]] is a 4 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=2O99 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2O99 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOA:GLYCOLIC+ACID'>GOA</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]] 1.7Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOA:GLYCOLIC+ACID'>GOA</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2o9a|2o9a]]</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=2o99 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o99 OCA], [https://pdbe.org/2o99 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2o99 RCSB], [https://www.ebi.ac.uk/pdbsum/2o99 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2o99 ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2o99 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2o99 OCA], [http://pdbe.org/2o99 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2o99 RCSB], [http://www.ebi.ac.uk/pdbsum/2o99 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2o99 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ICLR_ECOLI ICLR_ECOLI]] Regulation of the glyoxylate bypass operon (aceBAK), which encodes isocitrate lyase, malate synthase as well as isocitrate dehydrogenase kinase/phosphorylase. Glyoxylate disrupts the interaction with the promoter by favoring the inactive dimeric form. Pyruvate enhances promoter binding by stabilizing the tetrameric form. | + | [https://www.uniprot.org/uniprot/ICLR_ECOLI ICLR_ECOLI] Regulation of the glyoxylate bypass operon (aceBAK), which encodes isocitrate lyase, malate synthase as well as isocitrate dehydrogenase kinase/phosphorylase. Glyoxylate disrupts the interaction with the promoter by favoring the inactive dimeric form. Pyruvate enhances promoter binding by stabilizing the tetrameric form. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 2o99" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 2o99" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Transcriptional activator 3D structures|Transcriptional activator 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: Evdokimova, E]] | + | [[Category: Evdokimova E]] |
| - | [[Category: Ezersky, A]] | + | [[Category: Ezersky A]] |
| - | [[Category: Kudritska, M]] | + | [[Category: Kudritska M]] |
| - | [[Category: Lunin, V V]] | + | [[Category: Lunin VV]] |
| - | [[Category: Savchenko, A]] | + | [[Category: Savchenko A]] |
| - | [[Category: Dna binding protein]]
| + | |
| - | [[Category: Iclr]]
| + | |
| Structural highlights
Function
ICLR_ECOLI Regulation of the glyoxylate bypass operon (aceBAK), which encodes isocitrate lyase, malate synthase as well as isocitrate dehydrogenase kinase/phosphorylase. Glyoxylate disrupts the interaction with the promoter by favoring the inactive dimeric form. Pyruvate enhances promoter binding by stabilizing the tetrameric form.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The Escherichia coli isocitrate lyase regulator (IclR) regulates the expression of the glyoxylate bypass operon (aceBAK). Founding member of a large family of common fold transcriptional regulators, IclR comprises a DNA binding domain that interacts with the operator sequence and a C-terminal domain (C-IclR) that binds a hitherto unknown small molecule. We screened a chemical library of more than 150 metabolic scaffolds using a high-throughput protein stability assay to identify molecules that bind IclR and then tested the active compounds in in vitro assays of operator binding. Glyoxylate and pyruvate, identified by this method, bound the C-IclR domain with KD values of 0.9+/-0.2 and 156.2+/-7.9 microM, as defined by isothermal titration calorimetry. Both compounds altered IclR interactions with operator DNA in electrophoretic mobility shift assays but showed an antagonistic effect. Glyoxylate disrupted the formation of the IclR/operator complex in vitro by favoring the inactive dimeric state of the protein, whereas pyruvate increased the binding of IclR to the aceBAK promoter by stabilizing the active tetrameric form of the protein. Structures of the C-IclR domain alone and in complex with each effector were determined at 2.3 A, confirming the binding of both molecules in the effector recognition site previously characterized for the other representative of the family, the E. coli AllR regulator. Site-directed mutagenesis demonstrated the importance of hydrophobic patch formed by Met-146, Leu-154, Leu-220, and Leu-143 in interactions with effector molecules. In general, our strategy of combining chemical screens with functional assays and structural studies has uncovered two small molecules with antagonistic effects that regulate the IclR-dependent transcription of the aceBAK operon.
Glyoxylate and pyruvate are antagonistic effectors of the Escherichia coli IclR transcriptional regulator.,Lorca GL, Ezersky A, Lunin VV, Walker JR, Altamentova S, Evdokimova E, Vedadi M, Bochkarev A, Savchenko A J Biol Chem. 2007 Jun 1;282(22):16476-91. Epub 2007 Apr 10. PMID:17426033[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Lorca GL, Ezersky A, Lunin VV, Walker JR, Altamentova S, Evdokimova E, Vedadi M, Bochkarev A, Savchenko A. Glyoxylate and pyruvate are antagonistic effectors of the Escherichia coli IclR transcriptional regulator. J Biol Chem. 2007 Jun 1;282(22):16476-91. Epub 2007 Apr 10. PMID:17426033 doi:10.1074/jbc.M610838200
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