3elc: Difference between revisions
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<StructureSection load='3elc' size='340' side='right' caption='[[3elc]], [[Resolution|resolution]] 2.50Å' scene=''> | <StructureSection load='3elc' size='340' side='right' caption='[[3elc]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3elc]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3elc]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ELC OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ELC FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F01:4-AMINO-1-[(2R,3R,4S,5R)-3,4-DIHYDROXY-5-(HYDROXYMETHYL)OXOLAN-2-YL]-5-FLUORO-PYRIMIDIN-2-ONE'>F01</scene>, <scene name='pdbligand=GPP:GERANYL+DIPHOSPHATE'>GPP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=F01:4-AMINO-1-[(2R,3R,4S,5R)-3,4-DIHYDROXY-5-(HYDROXYMETHYL)OXOLAN-2-YL]-5-FLUORO-PYRIMIDIN-2-ONE'>F01</scene>, <scene name='pdbligand=GPP:GERANYL+DIPHOSPHATE'>GPP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ispF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ispF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83333 ECOLI])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/2-C-methyl-D-erythritol_2,4-cyclodiphosphate_synthase 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.6.1.12 4.6.1.12] </span></td></tr> | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/2-C-methyl-D-erythritol_2,4-cyclodiphosphate_synthase 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=4.6.1.12 4.6.1.12] </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=3elc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3elc OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3elc RCSB], [http://www.ebi.ac.uk/pdbsum/3elc PDBsum]</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=3elc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3elc OCA], [http://pdbe.org/3elc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3elc RCSB], [http://www.ebi.ac.uk/pdbsum/3elc PDBsum]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
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<text>to colour the structure by Evolutionary Conservation</text> | <text>to colour the structure by Evolutionary Conservation</text> | ||
</jmolCheckbox> | </jmolCheckbox> | ||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/ | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3elc ConSurf]. | ||
<div style="clear:both"></div> | <div style="clear:both"></div> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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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 3elc" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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</StructureSection> | </StructureSection> | ||
[[Category: 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase]] | [[Category: 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase]] | ||
[[Category: | [[Category: Ecoli]] | ||
[[Category: Hunter, W N]] | [[Category: Hunter, W N]] | ||
[[Category: Ramsden, N L]] | [[Category: Ramsden, N L]] | ||
Revision as of 11:56, 8 February 2016
Crystal structure of 2C-methyl-D-erythritol 2,4-clycodiphosphate synthase complexed with ligandCrystal structure of 2C-methyl-D-erythritol 2,4-clycodiphosphate synthase complexed with ligand
Structural highlights
Function[ISPF_ECOLI] Involved in the biosynthesis of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP), two major building blocks of isoprenoid compounds. Catalyzes the conversion of 4-diphosphocytidyl-2-C-methyl-D-erythritol 2-phosphate (CDP-ME2P) to 2-C-methyl-D-erythritol 2,4-cyclodiphosphate (ME-CPP) with a corresponding release of cytidine 5-monophosphate (CMP). Also converts 4-diphosphocytidyl-2-C-methyl-D-erythritol into 2-C-methyl-D-erythritol 3,4-cyclophosphate and CMP.[1] [2] 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 PubMedThe nonmevalonate route to isoprenoid biosynthesis is essential in Gram-negative bacteria and apicomplexan parasites. The enzymes of this pathway are absent from mammals, contributing to their appeal as chemotherapeutic targets. One enzyme, 2C-methyl-d-erythritol-2,4-cyclodiphosphate synthase (IspF), has been validated as a target by genetic approaches in bacteria. Virtual screening against Escherichia coli IspF (EcIspF) was performed by combining a hierarchical filtering methodology with molecular docking. Docked compounds were inspected and 10 selected for experimental validation. A surface plasmon resonance assay was developed and two weak ligands identified. Crystal structures of EcIspF complexes were determined to support rational ligand development. Cytosine analogues and Zn(2+)-binding moieties were characterized. One of the putative Zn(2+)-binding compounds gave the lowest measured K(D) to date (1.92 +/- 0.18 muM). These data provide a framework for the development of IspF inhibitors to generate lead compounds of therapeutic potential against microbial pathogens. A structure-based approach to ligand discovery for 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase: a target for antimicrobial therapy.,Ramsden NL, Buetow L, Dawson A, Kemp LA, Ulaganathan V, Brenk R, Klebe G, Hunter WN J Med Chem. 2009 Apr 23;52(8):2531-42. PMID:19320487[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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