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| | ==Crystal Structure of Fe(II)-HppE with alternative substrate (S)-1-HPP== | | ==Crystal Structure of Fe(II)-HppE with alternative substrate (S)-1-HPP== |
| - | <StructureSection load='4j1x' size='340' side='right' caption='[[4j1x]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='4j1x' size='340' side='right'caption='[[4j1x]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4j1x]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/"actinomyces_wedmorensis"_milard_and_burr_1926 "actinomyces wedmorensis" milard and burr 1926]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J1X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J1X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4j1x]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_wedmorensis Streptomyces wedmorensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J1X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4J1X FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1JJ:[(1S)-1-HYDROXYPROPYL]PHOSPHONIC+ACID'>1JJ</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1JJ:[(1S)-1-HYDROXYPROPYL]PHOSPHONIC+ACID'>1JJ</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4j1w|4j1w]], [[3scf|3scf]], [[3scg|3scg]], [[1zz8|1zz8]], [[1zz7|1zz7]]</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=4j1x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j1x OCA], [https://pdbe.org/4j1x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4j1x RCSB], [https://www.ebi.ac.uk/pdbsum/4j1x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4j1x ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">fom4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=43759 "Actinomyces wedmorensis" Milard and Burr 1926])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4j1x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j1x OCA], [http://pdbe.org/4j1x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4j1x RCSB], [http://www.ebi.ac.uk/pdbsum/4j1x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4j1x ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/HPPE_STRWE HPPE_STRWE] 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:16015285</ref> <ref>PMID:16186494</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4j1x" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4j1x" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Epoxidase 3D structures|Epoxidase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Actinomyces wedmorensis milard and burr 1926]] | + | [[Category: Large Structures]] |
| - | [[Category: Dey, M]] | + | [[Category: Streptomyces wedmorensis]] |
| - | [[Category: Drennan, C L]] | + | [[Category: Dey M]] |
| - | [[Category: Cupin fold]] | + | [[Category: Drennan CL]] |
| - | [[Category: Hydroxypropylphosphonic acid epoxidase]]
| + | |
| - | [[Category: Keto product]]
| + | |
| - | [[Category: Metal binding protein]]
| + | |
| - | [[Category: Mononuclear non-heme iron enzyme]]
| + | |
| - | [[Category: Phosphono migration]]
| + | |
| Structural highlights
Function
HPPE_STRWE 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.[1] [2]
Publication Abstract from PubMed
(S)-2-hydroxypropylphosphonate ((S)-2-HPP) epoxidase (HppE) is a mononuclear non-haem-iron-dependent enzyme responsible for the final step in the biosynthesis of the clinically useful antibiotic fosfomycin. Enzymes of this class typically catalyse oxygenation reactions that proceed via the formation of substrate radical intermediates. By contrast, HppE catalyses an unusual dehydrogenation reaction while converting the secondary alcohol of (S)-2-HPP to the epoxide ring of fosfomycin. Here we show that HppE also catalyses a biologically unprecedented 1,2-phosphono migration with the alternative substrate (R)-1-HPP. This transformation probably involves an intermediary carbocation, based on observations with additional substrate analogues, such as (1R)-1-hydroxyl-2-aminopropylphosphonate, and model reactions for both radical- and carbocation-mediated migration. The ability of HppE to catalyse distinct reactions depending on the regio- and stereochemical properties of the substrate is given a structural basis using X-ray crystallography. These results provide compelling evidence for the formation of a substrate-derived cation intermediate in the catalytic cycle of a mononuclear non-haem-iron-dependent enzyme. The underlying chemistry of this unusual phosphono migration may represent a new paradigm for the in vivo construction of phosphonate-containing natural products that can be exploited for the preparation of new phosphonate derivatives.
Mechanistic studies of an unprecedented enzyme-catalysed 1,2-phosphono-migration reaction.,Chang WC, Dey M, Liu P, Mansoorabadi SO, Moon SJ, Zhao ZK, Drennan CL, Liu HW Nature. 2013 Apr 4;496(7443):114-8. doi: 10.1038/nature11998. PMID:23552950[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Higgins LJ, Yan F, Liu P, Liu HW, Drennan CL. Structural insight into antibiotic fosfomycin biosynthesis by a mononuclear iron enzyme. Nature. 2005 Oct 6;437(7060):838-44. Epub 2005 Jul 13. PMID:16015285 doi:http://dx.doi.org/10.1038/nature03924
- ↑ McLuskey K, Cameron S, Hammerschmidt F, Hunter WN. Structure and reactivity of hydroxypropylphosphonic acid epoxidase in fosfomycin biosynthesis by a cation- and flavin-dependent mechanism. Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14221-6. Epub 2005 Sep 26. PMID:16186494
- ↑ Chang WC, Dey M, Liu P, Mansoorabadi SO, Moon SJ, Zhao ZK, Drennan CL, Liu HW. Mechanistic studies of an unprecedented enzyme-catalysed 1,2-phosphono-migration reaction. Nature. 2013 Apr 4;496(7443):114-8. doi: 10.1038/nature11998. PMID:23552950 doi:http://dx.doi.org/10.1038/nature11998
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