1h48
From Proteopedia
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| - | [[Image:1h48.gif|left|200px]]<br /> | + | [[Image:1h48.gif|left|200px]]<br /><applet load="1h48" size="450" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1h48" size="450" color="white" frame="true" align="right" spinBox="true" | + | |
caption="1h48, resolution 2.30Å" /> | caption="1h48, resolution 2.30Å" /> | ||
'''THE STRUCTURE OF 2C-METHYL-D-ERYTHRITOL 2,4-CYCLODIPHOSPHATE SYNTHASE IN COMPLEX WITH CMP AND PRODUCT'''<br /> | '''THE STRUCTURE OF 2C-METHYL-D-ERYTHRITOL 2,4-CYCLODIPHOSPHATE SYNTHASE IN COMPLEX WITH CMP AND PRODUCT'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 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 ZN, MN, CDI, C5P and GPP 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] | + | 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 ZN, MN, CDI, C5P and GPP 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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1H48 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: lyase]] | [[Category: lyase]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Dec 18 15:58:22 2007'' |
Revision as of 13:48, 18 December 2007
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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 with ZN, MN, CDI, C5P and GPP as ligands. Active as 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, with EC number 4.6.1.12 Known structural/functional Site: . 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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