1h48

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[[Image:1h48.gif|left|200px]]<br /><applet load="1h48" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1h48.gif|left|200px]]
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caption="1h48, resolution 2.30&Aring;" />
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'''THE STRUCTURE OF 2C-METHYL-D-ERYTHRITOL 2,4-CYCLODIPHOSPHATE SYNTHASE IN COMPLEX WITH CMP AND PRODUCT'''<br />
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{{Structure
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|PDB= 1h48 |SIZE=350|CAPTION= <scene name='initialview01'>1h48</scene>, resolution 2.30&Aring;
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|SITE= <scene name='pdbsite=AC1:Mn+Binding+Site+For+Chain+D'>AC1</scene>
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|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=CDI:2C-METHYL-D-ERYTHRITOL+2,4-CYCLODIPHOSPHATE'>CDI</scene>, <scene name='pdbligand=C5P:CYTIDINE-5'-MONOPHOSPHATE'>C5P</scene> and <scene name='pdbligand=GPP:GERANYL DIPHOSPHATE'>GPP</scene>
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|ACTIVITY= [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]
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|GENE=
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}}
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'''THE STRUCTURE OF 2C-METHYL-D-ERYTHRITOL 2,4-CYCLODIPHOSPHATE SYNTHASE IN COMPLEX WITH CMP AND PRODUCT'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1H48 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=MN:'>MN</scene>, <scene name='pdbligand=CDI:'>CDI</scene>, <scene name='pdbligand=C5P:'>C5P</scene> and <scene name='pdbligand=GPP:'>GPP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Site: <scene name='pdbsite=AC1:Mn+Binding+Site+For+Chain+D'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H48 OCA].
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1H48 is a [[Single protein]] structure of 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].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15608374 15608374]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/15608374 15608374]
[[Category: 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase]]
[[Category: 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase]]
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
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[[Category: lyase]]
[[Category: lyase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:57:16 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:31:59 2008''

Revision as of 09:32, 20 March 2008


PDB ID 1h48

Drag the structure with the mouse to rotate
, resolution 2.30Å
Sites:
Ligands: , , , and
Activity: 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, with EC number 4.6.1.12
Coordinates: save as pdb, mmCIF, xml



THE STRUCTURE OF 2C-METHYL-D-ERYTHRITOL 2,4-CYCLODIPHOSPHATE SYNTHASE IN COMPLEX WITH CMP AND PRODUCT


Overview

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.

About this Structure

1H48 is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

Reference

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

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