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1onp

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[[Image:1onp.gif|left|200px]]
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{{STRUCTURE_1onp| PDB=1onp | SCENE= }}
{{STRUCTURE_1onp| PDB=1onp | SCENE= }}
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'''IspC complex with Mn2+ and fosmidomycin'''
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===IspC complex with Mn2+ and fosmidomycin===
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==Overview==
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2-C-Methyl-d-erythritol 4-phosphate synthase (IspC) is the first enzyme committed to isoprenoid biosynthesis in the methylerythritol phosphate pathway, which represents an alternative route to the classical mevalonate pathway. As it is present in many pathogens and plants, but not in man, this pathway has attracted considerable interest as a target for novel antibiotics and herbicides. Fosmidomycin represents a specific high-affinity inhibitor of IspC. Very recently, its anti-malaria activity in man has been demonstrated in clinical trials. Here, we present the crystal structure of Escherichia coli IspC in complex with manganese and fosmidomycin at 2.5 A resolution. The (N-formyl-N-hydroxy)amino group provides two oxygen ligands to manganese that is present in a distorted octahedral coordination, whereas the phosphonate group is anchored in a specific pocket by numerous hydrogen bonds. Both sites are connected by a spacer of three methylene groups. The substrate molecule, 1-d-deoxyxylulose 5-phosphate, can be superimposed onto fosmidomycin, explaining the stereochemical course of the reaction.
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The line below this paragraph, {{ABSTRACT_PUBMED_12621040}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 12621040 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12621040}}
==About this Structure==
==About this Structure==
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[[Category: Ispc]]
[[Category: Ispc]]
[[Category: Mevalonate-independent pathway]]
[[Category: Mevalonate-independent pathway]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 04:04:32 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 22:43:14 2008''

Revision as of 19:43, 27 July 2008

Image:1onp.png

Template:STRUCTURE 1onp

IspC complex with Mn2+ and fosmidomycin

Template:ABSTRACT PUBMED 12621040

About this Structure

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

Reference

Structural basis of fosmidomycin action revealed by the complex with 2-C-methyl-D-erythritol 4-phosphate synthase (IspC). Implications for the catalytic mechanism and anti-malaria drug development., Steinbacher S, Kaiser J, Eisenreich W, Huber R, Bacher A, Rohdich F, J Biol Chem. 2003 May 16;278(20):18401-7. Epub 2003 Mar 5. PMID:12621040

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