5u55

Psf4 in complex with Mn2+ and (S)-2-HPP

spinqualitylabelsall models 5u55, resolution 2.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5u55 is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MN, S0H Related: 5u57, 5u58, 5u5d Activity: (S)-2-hydroxypropylphosphonic acid epoxidase, with EC number 1.11.1.23 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [HPPE_PSESX] Non-heme-dependent dioxygenase that catalyzes the oxidative epoxidation of (S)-2-hydroxypropylphosphonate into (1R,2S)-epoxypropylphosphonate, the final step in the biosynthesis of fosfomycin antibiotic. Publication Abstract from PubMed The broad-spectrum phosphonate antibiotic fosfomycin is currently in use for clinical treatment of infections caused by both Gram-positive and Gram-negative uropathogens. The antibiotic is biosynthesized by various streptomycetes, as well as by pseudomonads. Notably, the biosynthetic strategies used by the two genera share only two steps: the first step in which primary metabolite phosphoenolpyruvate (PEP) is converted to phosphonopyruvate (PnPy) and the terminal step in which 2-hydroxypropylphosphonate (2-HPP) is converted to fosfomycin. Otherwise, distinct enzymatic paths are employed. Here, we biochemically confirm the last two steps in the fosfomycin biosynthetic pathway of Pseudomonas syringae PB-5123, showing that Psf3 performs the reduction of 2-oxopropylphosphonate (2-OPP) to (S)-2-HPP, followed by the Psf4-catalyzed epoxidation of (S)-2-HPP to fosfomycin. Psf4 can also accept (R)-2-HPP as a substrate but instead performs an oxidation to make 2-OPP. We show that the combined activities of Psf3 and Psf4 can be used to convert racemic 2-HPP to fosfomycin in an enantioconvergent process. X-ray structures of each enzyme with bound substrates provide insights into the stereospecificity of each conversion. These studies shed light on the reaction mechanisms of the two terminal enzymes in a distinct pathway employed by pseudomonads for the production of a potent antimicrobial agent. Characterization of Two Late-Stage Enzymes Involved in Fosfomycin Biosynthesis in Pseudomonads.,Olivares P, Ulrich EC, Chekan JR, van der Donk WA, Nair SK ACS Chem Biol. 2016 Dec 27. doi: 10.1021/acschembio.6b00939. PMID:27977135 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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