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| | <StructureSection load='5u5d' size='340' side='right'caption='[[5u5d]], [[Resolution|resolution]] 2.49Å' scene=''> | | <StructureSection load='5u5d' size='340' side='right'caption='[[5u5d]], [[Resolution|resolution]] 2.49Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5u5d]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_19310 Atcc 19310]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U5D OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5U5D FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5u5d]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_syringae Pseudomonas syringae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U5D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U5D FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=TB6:[(2R)-2-HYDROXYPROPYL]PHOSPHONIC+ACID'>TB6</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.49Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5u57|5u57]], [[5u58|5u58]], [[5u55|5u55]], [[5u5g|5u5g]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=TB6:[(2R)-2-HYDROXYPROPYL]PHOSPHONIC+ACID'>TB6</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">hppE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=317 ATCC 19310])</td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5u5d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u5d OCA], [https://pdbe.org/5u5d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u5d RCSB], [https://www.ebi.ac.uk/pdbsum/5u5d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u5d ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/(S)-2-hydroxypropylphosphonic_acid_epoxidase (S)-2-hydroxypropylphosphonic acid epoxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.23 1.11.1.23] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5u5d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u5d OCA], [http://pdbe.org/5u5d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u5d RCSB], [http://www.ebi.ac.uk/pdbsum/5u5d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u5d ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HPPE_PSESX 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.<ref>PMID:18656958</ref> | + | [https://www.uniprot.org/uniprot/HPPE_PSESX 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.<ref>PMID:18656958</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == 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.
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| - | 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<ref>PMID:27977135</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 5u5d" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 19310]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chekan, J R]] | + | [[Category: Pseudomonas syringae]] |
| - | [[Category: Nair, S K]] | + | [[Category: Chekan JR]] |
| - | [[Category: Epoxidase]] | + | [[Category: Nair SK]] |
| - | [[Category: Fosfomycin]]
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| - | [[Category: Oxidase]]
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| - | [[Category: Oxidoreductase]]
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