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| | ==Crystal structure of 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase from Burkholderia pseudomallei in complex with a fragment-nucleoside fusion D000161829== | | ==Crystal structure of 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase from Burkholderia pseudomallei in complex with a fragment-nucleoside fusion D000161829== |
| - | <StructureSection load='3ke1' size='340' side='right' caption='[[3ke1]], [[Resolution|resolution]] 2.05Å' scene=''> | + | <StructureSection load='3ke1' size='340' side='right'caption='[[3ke1]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ke1]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_pseudomallei"_whitmore_1913 "bacillus pseudomallei" whitmore 1913]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KE1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3KE1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ke1]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_pseudomallei Burkholderia pseudomallei]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3KE1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3KE1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=829:5-DEOXY-5-[(PYRIDIN-4-YLCARBONYL)AMINO]CYTIDINE'>829</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 2.05Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ike|3ike]], [[3jvh|3jvh]], [[3k2x|3k2x]], [[3k14|3k14]], [[3ikf|3ikf]], [[3ieq|3ieq]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=829:5-DEOXY-5-[(PYRIDIN-4-YLCARBONYL)AMINO]CYTIDINE'>829</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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, mecS, BPSL2098 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=28450 "Bacillus pseudomallei" Whitmore 1913])</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=3ke1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ke1 OCA], [https://pdbe.org/3ke1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ke1 RCSB], [https://www.ebi.ac.uk/pdbsum/3ke1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ke1 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/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=3ke1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ke1 OCA], [http://pdbe.org/3ke1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ke1 RCSB], [http://www.ebi.ac.uk/pdbsum/3ke1 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ISPF_BURPS ISPF_BURPS]] 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) (By similarity).[HAMAP-Rule:MF_00107] | + | [https://www.uniprot.org/uniprot/ISPF_BURP1 ISPF_BURP1] 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) (By similarity).[HAMAP-Rule:MF_00107] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ke/3ke1_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ke/3ke1_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
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| | ==See Also== | | ==See Also== |
| - | *[[MECDP synthase|MECDP synthase]] | + | *[[MECDP synthase 3D structures|MECDP synthase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus pseudomallei whitmore 1913]] | + | [[Category: Burkholderia pseudomallei]] |
| - | [[Category: 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase]] | + | [[Category: Large Structures]] |
| - | [[Category: Structural genomic]]
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| - | [[Category: D000161829]]
| + | |
| - | [[Category: Fbdd]]
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| - | [[Category: Fragment crystallography]]
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| - | [[Category: Fragment-based drug-design]]
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| - | [[Category: Isoprene biosynthesis]]
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| - | [[Category: Lyase]]
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| - | [[Category: Metal-binding]]
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| - | [[Category: Niaid]]
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| - | [[Category: Nucleoside analog]]
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| - | [[Category: Ssgcid]]
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| Structural highlights
Function
ISPF_BURP1 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) (By similarity).[HAMAP-Rule:MF_00107]
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
Published biological data suggest that the methyl erythritol phosphate (MEP) pathway, a non-mevalonate isoprenoid biosynthetic pathway, is essential for certain bacteria and other infectious disease organisms. One highly conserved enzyme in the MEP pathway is 2C-methyl-d-erythritol 2,4-cyclodiphosphate synthase (IspF). Fragment-bound complexes of IspF from Burkholderia pseudomallei were used to design and synthesize a series of molecules linking the cytidine moiety to different zinc pocket fragment binders. Testing by surface plasmon resonance (SPR) found one molecule in the series to possess binding affinity equal to that of cytidine diphosphate, despite lacking any metal-coordinating phosphate groups. Close inspection of the SPR data suggest different binding stoichiometries between IspF and test compounds. Crystallographic analysis shows important variations between the binding mode of one synthesized compound and the pose of the bound fragment from which it was designed. The binding modes of these molecules add to our structural knowledge base for IspF and suggest future refinements in this compound series.
Cytidine derivatives as IspF inhibitors of Burkolderia pseudomallei.,Zhang Z, Jakkaraju S, Blain J, Gogol K, Zhao L, Hartley RC, Karlsson CA, Staker BL, Edwards TE, Stewart LJ, Myler PJ, Clare M, Begley DW, Horn JR, Hagen TJ Bioorg Med Chem Lett. 2013 Dec 15;23(24):6860-3. doi: 10.1016/j.bmcl.2013.09.101., Epub 2013 Oct 8. PMID:24157367[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Zhang Z, Jakkaraju S, Blain J, Gogol K, Zhao L, Hartley RC, Karlsson CA, Staker BL, Edwards TE, Stewart LJ, Myler PJ, Clare M, Begley DW, Horn JR, Hagen TJ. Cytidine derivatives as IspF inhibitors of Burkolderia pseudomallei. Bioorg Med Chem Lett. 2013 Dec 15;23(24):6860-3. doi: 10.1016/j.bmcl.2013.09.101., Epub 2013 Oct 8. PMID:24157367 doi:http://dx.doi.org/10.1016/j.bmcl.2013.09.101
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