2p7p

Crystal structure of genomically encoded fosfomycin resistance protein, FosX, from Listeria monocytogenes complexed with MN(II) and sulfate ion

spinqualitylabelsall models 2p7p, resolution 2.17Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2p7p is a 6 chain structure with sequence from Listeria monocytogenes EGD-e. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.17Å Ligands: MN, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function FOSX_LISMO Catalyzes the hydration of fosfomycin. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed The fosfomycin resistance protein, FosX, catalyzes the hydration of the antibiotic fosfomycin, (1R,2S)-epoxypropylphosphonic acid. Genes encoding the enzyme are found in several pathogenic microorganisms. The structure and mechanism of action of the genomically encoded FosX enzyme from Listeria monocytogenes (FosXLMATCC) obtained from the American Type Culture Collection are reported. The gene harbors 31 point mutations, and as a consequence, the protein differs in 10 amino acid residues from the previously reported FosX encoded in the genome of the EGD strain of L. monocytogenes (FosXLMEGD). The FosXLMATCC enzyme is shown to catalyze the addition of water to the C1 position of the antibiotic with inversion of configuration at C1. The reaction involves Mn(II) activation of the oxirane oxygen and E44 acting as a general base. The structure of the enzyme has been determined from six different crystal forms of the protein. The structures of the enzyme without metal bound are similar but differ in the loop regions. Perhaps the most informative structure is the one with the product bound. This structure shows that the phosphonate group of the product is bound in an orientation that is different than that of fosfomycin bound to the related enzyme, FosA. The implication is that the substrate may also be bound in a different orientation in FosX. A high-resolution structure (1.44 A resolution) of the enzyme reveals a unique conformation in which the C-terminal tail of the protein coordinates to the Mn(II) center via the carboxylate of E126. The kinetic characterization of the E126Q mutant indicates that this conformation of the protein is probably not relevant to the function of the enzyme. Kinetic analysis of mutants of active site residue E44 is consistent with its proposed roll as a general base catalyst in the addition of water to the antibiotic. Structure and mechanism of the genomically encoded fosfomycin resistance protein, FosX, from Listeria monocytogenes.,Fillgrove KL, Pakhomova S, Schaab MR, Newcomer ME, Armstrong RN Biochemistry. 2007 Jul 10;46(27):8110-20. Epub 2007 Jun 13. PMID:17567049 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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