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6d3q
From Proteopedia
(Difference between revisions)
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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. 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 [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> |
</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='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> | ||
| + | <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='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='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'>[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> | <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> | ||
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== 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. | [[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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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<ref>PMID:31745118</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6d3q" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Bacillus coli migula 1895]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Phosphopyruvate hydratase]] | [[Category: Phosphopyruvate hydratase]] | ||
Revision as of 10:03, 4 December 2019
Crystal structure of Escherichia coli enolase complexed with a natural inhibitor SF2312.
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