1q0h
From Proteopedia
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| - | [[Image:1q0h.gif|left|200px]] | + | [[Image:1q0h.gif|left|200px]] |
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| - | '''Crystal structure of selenomethionine-labelled DXR in complex with fosmidomycin''' | + | {{Structure |
| + | |PDB= 1q0h |SIZE=350|CAPTION= <scene name='initialview01'>1q0h</scene>, resolution 2.20Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=FOM:3-[FORMYL(HYDROXY)AMINO]PROPYLPHOSPHONIC+ACID'>FOM</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene> and <scene name='pdbligand=CIT:CITRIC ACID'>CIT</scene> | ||
| + | |ACTIVITY= [http://en.wikipedia.org/wiki/1-deoxy-D-xylulose-5-phosphate_reductoisomerase 1-deoxy-D-xylulose-5-phosphate reductoisomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.267 1.1.1.267] | ||
| + | |GENE= DXR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 Escherichia coli]) | ||
| + | }} | ||
| + | |||
| + | '''Crystal structure of selenomethionine-labelled DXR in complex with fosmidomycin''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1Q0H is a [ | + | 1Q0H 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=1Q0H OCA]. |
==Reference== | ==Reference== | ||
| - | The crystal structure of E.coli 1-deoxy-D-xylulose-5-phosphate reductoisomerase in a ternary complex with the antimalarial compound fosmidomycin and NADPH reveals a tight-binding closed enzyme conformation., Mac Sweeney A, Lange R, Fernandes RP, Schulz H, Dale GE, Douangamath A, Proteau PJ, Oefner C, J Mol Biol. 2005 Jan 7;345(1):115-27. PMID:[http:// | + | The crystal structure of E.coli 1-deoxy-D-xylulose-5-phosphate reductoisomerase in a ternary complex with the antimalarial compound fosmidomycin and NADPH reveals a tight-binding closed enzyme conformation., Mac Sweeney A, Lange R, Fernandes RP, Schulz H, Dale GE, Douangamath A, Proteau PJ, Oefner C, J Mol Biol. 2005 Jan 7;345(1):115-27. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15567415 15567415] |
[[Category: 1-deoxy-D-xylulose-5-phosphate reductoisomerase]] | [[Category: 1-deoxy-D-xylulose-5-phosphate reductoisomerase]] | ||
[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
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[[Category: oxidoreductase]] | [[Category: oxidoreductase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:31:23 2008'' |
Revision as of 11:31, 20 March 2008
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| , resolution 2.20Å | |||||||
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| Ligands: | , and | ||||||
| Gene: | DXR (Escherichia coli) | ||||||
| Activity: | 1-deoxy-D-xylulose-5-phosphate reductoisomerase, with EC number 1.1.1.267 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of selenomethionine-labelled DXR in complex with fosmidomycin
Overview
The key enzyme in the non-mevalonate pathway of isoprenoid biosynthesis, 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) has been shown to be the target enzyme of fosmidomycin, an antimalarial, antibacterial and herbicidal compound. Here we report the crystal structure of selenomethionine-labelled Escherichia coli DXR in a ternary complex with NADPH and fosmidomycin at 2.2 A resolution. The structure reveals a considerable conformational rearrangement upon fosmidomycin binding and provides insights into the slow, tight binding inhibition mode of the inhibitor. Although the inhibitor displays an unusual non-metal mediated mode of inhibition, which is an artefact most likely due to the low metal affinity of DXR at the pH used for crystallization, the structural data add valuable information for the rational design of novel DXR inhibitors. Using this structure together with the published structural data and the 1.9 A crystal structure of DXR in a ternary complex with NADPH and the substrate 1-deoxy-D-xylulose 5-phosphate, a model for the physiologically relevant tight-binding mode of inhibition is proposed. The structure of the substrate complex must be interpreted with caution due to the presence of a second diastereomer in the active site.
About this Structure
1Q0H is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
The crystal structure of E.coli 1-deoxy-D-xylulose-5-phosphate reductoisomerase in a ternary complex with the antimalarial compound fosmidomycin and NADPH reveals a tight-binding closed enzyme conformation., Mac Sweeney A, Lange R, Fernandes RP, Schulz H, Dale GE, Douangamath A, Proteau PJ, Oefner C, J Mol Biol. 2005 Jan 7;345(1):115-27. PMID:15567415
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