1q0h
From Proteopedia
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'''Crystal structure of selenomethionine-labelled DXR in complex with fosmidomycin''' | '''Crystal structure of selenomethionine-labelled DXR in complex with fosmidomycin''' | ||
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[[Category: Surivet, J P.]] | [[Category: Surivet, J P.]] | ||
[[Category: Sweeney, A Mac.]] | [[Category: Sweeney, A Mac.]] | ||
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| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:43:02 2008'' | |
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Revision as of 02:43, 3 May 2008
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 Page seeded by OCA on Sat May 3 05:43:02 2008
