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| | <StructureSection load='1yqn' size='340' side='right'caption='[[1yqn]], [[Resolution|resolution]] 3.11Å' scene=''> | | <StructureSection load='1yqn' size='340' side='right'caption='[[1yqn]], [[Resolution|resolution]] 3.11Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1yqn]] is a 1 chain structure with sequence from [https://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=1YQN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YQN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1yqn]] is a 1 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=1YQN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1YQN FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CDP:CYTIDINE-5-DIPHOSPHATE'>CDP</scene>, <scene name='pdbligand=GPP:GERANYL+DIPHOSPHATE'>GPP</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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]] 3.11Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1gx1|1gx1]], [[1h47|1h47]], [[1h48|1h48]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CDP:CYTIDINE-5-DIPHOSPHATE'>CDP</scene>, <scene name='pdbligand=GPP:GERANYL+DIPHOSPHATE'>GPP</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</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 ([https://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'>[https://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 [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=1yqn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yqn OCA], [https://pdbe.org/1yqn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yqn RCSB], [https://www.ebi.ac.uk/pdbsum/1yqn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yqn ProSAT]</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=1yqn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yqn OCA], [https://pdbe.org/1yqn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1yqn RCSB], [https://www.ebi.ac.uk/pdbsum/1yqn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1yqn ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/ISPF_ECOLI 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.<ref>PMID:10694574</ref> <ref>PMID:22839733</ref>
| + | [https://www.uniprot.org/uniprot/ISPF_ECOLI 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.<ref>PMID:10694574</ref> <ref>PMID:22839733</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillus coli migula 1895]] | + | [[Category: Escherichia coli]] |
| - | [[Category: 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hunter, W N]] | + | [[Category: Hunter WN]] |
| - | [[Category: Kemp, L E]] | + | [[Category: Kemp LE]] |
| - | [[Category: Ramsden, N]] | + | [[Category: Ramsden N]] |
| - | [[Category: Sgraja, T]] | + | [[Category: Sgraja T]] |
| - | [[Category: 2c-methyl-d-erythriol-2]]
| + | |
| - | [[Category: Alpha-beta protein]]
| + | |
| - | [[Category: Lyase]]
| + | |
| 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 PubMed
The essential enzyme 2C-methyl-D-erythritol-2,4-cyclodiphosphate (MECP) synthase, found in most eubacteria and the apicomplexan parasites, participates in isoprenoid-precursor biosynthesis and is a validated target for the development of broad-spectrum antimicrobial drugs. The structure and mechanism of the enzyme have been elucidated and the recent exciting finding that the enzyme actually binds diphosphate-containing isoprenoids at the interface formed by the three subunits that constitute the active protein suggests the possibility of feedback regulation of MECP synthase. To investigate such a possibility, a form of the enzyme was sought that did not bind these ligands but which would retain the quaternary structure necessary to create the active site. Two amino acids, Arg142 and Glu144, in Escherichia coli MECP synthase were identified as contributing to ligand binding. Glu144 interacts directly with Arg142 and positions the basic residue to form two hydrogen bonds with the terminal phosphate group of the isoprenoid diphosphate ligand. This association occurs at the trimer interface and three of these arginines interact with the ligand phosphate group. A dual mutation was designed (Arg142 to methionine and Glu144 to leucine) to disrupt the electrostatic attractions between the enzyme and the phosphate group to investigate whether an enzyme without isoprenoid diphosphate could be obtained. A low-resolution crystal structure of the mutated MECP synthase Met142/Leu144 revealed that geranyl diphosphate was retained despite the removal of six hydrogen bonds normally formed with the enzyme. This indicates that these two hydrophilic residues on the surface of the enzyme are not major determinants of isoprenoid binding at the trimer interface but rather that hydrophobic interactions between the hydrocarbon tail and the core of the enzyme trimer dominate ligand binding.
A double mutation of Escherichia coli2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase disrupts six hydrogen bonds with, yet fails to prevent binding of, an isoprenoid diphosphate.,Sgraja T, Kemp LE, Ramsden N, Hunter WN Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Jul 1;61(Pt, 7):625-9. Epub 2005 Jun 30. PMID:16511114[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Herz S, Wungsintaweekul J, Schuhr CA, Hecht S, Luttgen H, Sagner S, Fellermeier M, Eisenreich W, Zenk MH, Bacher A, Rohdich F. Biosynthesis of terpenoids: YgbB protein converts 4-diphosphocytidyl-2C-methyl-D-erythritol 2-phosphate to 2C-methyl-D-erythritol 2,4-cyclodiphosphate. Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2486-90. PMID:10694574 doi:http://dx.doi.org/10.1073/pnas.040554697
- ↑ Bitok JK, Meyers CF. 2C-Methyl-d-erythritol 4-phosphate enhances and sustains cyclodiphosphate synthase IspF activity. ACS Chem Biol. 2012 Oct 19;7(10):1702-10. doi: 10.1021/cb300243w. Epub 2012 Aug, 6. PMID:22839733 doi:http://dx.doi.org/10.1021/cb300243w
- ↑ Sgraja T, Kemp LE, Ramsden N, Hunter WN. A double mutation of Escherichia coli2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase disrupts six hydrogen bonds with, yet fails to prevent binding of, an isoprenoid diphosphate. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2005 Jul 1;61(Pt, 7):625-9. Epub 2005 Jun 30. PMID:16511114 doi:10.1107/S1744309105018762
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