1h48

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{{STRUCTURE_1h48| PDB=1h48 | SCENE= }}
{{STRUCTURE_1h48| PDB=1h48 | SCENE= }}
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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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===THE STRUCTURE OF 2C-METHYL-D-ERYTHRITOL 2,4-CYCLODIPHOSPHATE SYNTHASE IN COMPLEX WITH CMP AND PRODUCT===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_15608374}}
==About this Structure==
==About this Structure==
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[[Category: Isoprenoid]]
[[Category: Isoprenoid]]
[[Category: Lyase]]
[[Category: Lyase]]
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Revision as of 03:35, 1 July 2008

Image:1h48.png

Template:STRUCTURE 1h48

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

Template:ABSTRACT PUBMED 15608374

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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