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1h48

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The structure of 2C-Methyl-D-erythritol 2,4-cyclodiphosphate synthase in complex with CMP and product

Structural highlights

1h48 is a 6 chain structure with sequence from Escherichia coli BL21. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Ligands:	, , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 discovery of a distinct metabolic pathway, the non-mevalonate or 1-deoxy-D-xylulose-5-phosphate (DOXP) pathway for isoprenoid precursor biosynthesis, in eubacteria and apicomplexan parasites has revealed a new set of potential drug targets. The emphasis of research on this pathway has been on delineating the intermediates and the biochemical and structural characterization of component enzymes. Two new monoclinic crystal forms of recombinant Escherichia coli 2C-methyl-D-erythritol-2,4-cyclodiphosphate (MECP) synthase cocrystallized with (i) CMP and (ii) CMP and MECP show well defined electron density at the subunit interface suggestive of an isoprenoid-like ligand. 31P NMR analysis of the recombinant protein sample indicates the presence of bound diphosphate species and electrospray mass spectrometry identifies a mixture of isopentenyl diphosphate (and/or dimethylallyl diphosphate), geranyl diphosphate and farnesyl diphosphate in an approximate ratio of 1:4:2. The most prevalent species, geranyl diphosphate, was successfully modelled into the electron density, revealing the important protein-ligand interactions that stabilize binding of the isoprenoid. The observation that MECP synthase binds three metabolites that are produced by enzymes two, three and four stages downstream in isoprenoid biosynthesis suggests that feedback regulation of the non-mevalonate pathway is possible.

The identification of isoprenoids that bind in the intersubunit cavity of Escherichia coli 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase by complementary biophysical methods.,Kemp LE, Alphey MS, Bond CS, Ferguson MA, Hecht S, Bacher A, Eisenreich W, Rohdich F, Hunter WN Acta Crystallogr D Biol Crystallogr. 2005 Jan;61(Pt 1):45-52. Epub 2004, Dec 17. PMID:15608374^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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
↑ Kemp LE, Alphey MS, Bond CS, Ferguson MA, Hecht S, Bacher A, Eisenreich W, Rohdich F, Hunter WN. The identification of isoprenoids that bind in the intersubunit cavity of Escherichia coli 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase by complementary biophysical methods. Acta Crystallogr D Biol Crystallogr. 2005 Jan;61(Pt 1):45-52. Epub 2004, Dec 17. PMID:15608374 doi:10.1107/S0907444904025971

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1h48"

@@ Line 1: / Line 1: @@
-==THE STRUCTURE OF 2C-METHYL-D-ERYTHRITOL 2,4-CYCLODIPHOSPHATE SYNTHASE IN COMPLEX WITH CMP AND PRODUCT==
-<StructureSection load='1h48' size='340' side='right' caption='[[1h48]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
+==The structure of 2C-Methyl-D-erythritol 2,4-cyclodiphosphate synthase in complex with CMP and product==
+<StructureSection load='1h48' size='340' side='right'caption='[[1h48]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1h48]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H48 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1H48 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1h48]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_BL21 Escherichia coli BL21]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H48 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1H48 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=C5P:CYTIDINE-5-MONOPHOSPHATE'>C5P</scene>, <scene name='pdbligand=CDI:2C-METHYL-D-ERYTHRITOL+2,4-CYCLODIPHOSPHATE'>CDI</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]] 2.3&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1gx1|1gx1]], [[1h47|1h47]], [[1jy8|1jy8]], [[1knj|1knj]], [[1knk|1knk]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C5P:CYTIDINE-5-MONOPHOSPHATE'>C5P</scene>, <scene name='pdbligand=CDI:2C-METHYL-D-ERYTHRITOL+2,4-CYCLODIPHOSPHATE'>CDI</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='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'>[https://proteopedia.org/fgij/fg.htm?mol=1h48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h48 OCA], [https://pdbe.org/1h48 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1h48 RCSB], [https://www.ebi.ac.uk/pdbsum/1h48 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1h48 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=1h48 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h48 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1h48 RCSB], [http://www.ebi.ac.uk/pdbsum/1h48 PDBsum]</span></td></tr>
 </table>
+== 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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h4/1h48_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/h4/1h48_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=1h48 ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 26: / Line 28: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1h48" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[MECDP synthase|MECDP synthase]]
+*[[MECDP synthase 3D structures|MECDP synthase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase]]
+[[Category: Escherichia coli BL21]]
-[[Category: Escherichia coli]]
+[[Category: Large Structures]]
-[[Category: Alphey, M S]]
+[[Category: Alphey MS]]
-[[Category: Bond, C S]]
+[[Category: Bond CS]]
-[[Category: Hunter, W N]]
+[[Category: Hunter WN]]
-[[Category: Kemp, L E]]
+[[Category: Kemp LE]]
-[[Category: Isoprene biosynthesis]]
-[[Category: Isoprenoid]]
-[[Category: Lyase]]
-[[Category: Synthase]]

1h48

From Proteopedia

Current revision

The structure of 2C-Methyl-D-erythritol 2,4-cyclodiphosphate synthase in complex with CMP and product

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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