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| | ==The structure of Hydroxypropylphosphonic acid epoxidase from S. wedmorenis.== | | ==The structure of Hydroxypropylphosphonic acid epoxidase from S. wedmorenis.== |
| - | <StructureSection load='2bnm' size='340' side='right' caption='[[2bnm]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='2bnm' size='340' side='right'caption='[[2bnm]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2bnm]] is a 2 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=2BNM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2BNM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2bnm]] is a 2 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=2BNM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2BNM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.7Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1zz9|1zz9]], [[1zz7|1zz7]], [[1zz8|1zz8]], [[1zz6|1zz6]], [[1zzc|1zzc]], [[1zzb|1zzb]], [[2bnn|2bnn]], [[2bno|2bno]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=2bnm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bnm OCA], [http://pdbe.org/2bnm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2bnm RCSB], [http://www.ebi.ac.uk/pdbsum/2bnm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2bnm ProSAT]</span></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=2bnm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2bnm OCA], [https://pdbe.org/2bnm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2bnm RCSB], [https://www.ebi.ac.uk/pdbsum/2bnm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2bnm 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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Epoxidase|Epoxidase]] | + | *[[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: Cameron, S]] | + | [[Category: Streptomyces wedmorensis]] |
| - | [[Category: Hunter, W N]] | + | [[Category: Cameron S]] |
| - | [[Category: McLuskey, K]] | + | [[Category: Hunter WN]] |
| - | [[Category: Cation-dependant]] | + | [[Category: McLuskey K]] |
| - | [[Category: Cupin]]
| + | |
| - | [[Category: Epoxidase]]
| + | |
| - | [[Category: Fosfomycin]]
| + | |
| - | [[Category: Hth]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Zinc]]
| + | |
| 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]
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 biosynthesis of fosfomycin, an oxirane antibiotic in clinical use, involves a unique epoxidation catalyzed by (S)-2-hydroxypropylphosphonic acid epoxidase (HPPE). The reaction is essentially dehydrogenation of a secondary alcohol. A high-resolution crystallographic analysis reveals that the HPPE subunit displays a two-domain combination. The C-terminal or catalytic domain has the cupin fold that binds a divalent cation, whereas the N-terminal domain carries a helix-turn-helix motif with putative DNA-binding helices positioned 34 A apart. The structure of HPPE serves as a model for numerous proteins, of ill-defined function, predicted to be transcription factors but carrying a cupin domain at the C terminus. Structure-reactivity analyses reveal conformational changes near the catalytic center driven by the presence or absence of ligand, that HPPE is a Zn(2+)/Fe(2+)-dependent epoxidase, proof that flavin mononucleotide is required for catalysis, and allow us to propose a simple mechanism that is compatible with previous experimental data. The participation of the redox inert Zn(2+) in the mechanism is surprising and indicates that Lewis acid properties of the metal ions are sufficient to polarize the substrate and, aided by flavin mononucleotide reduction, facilitate the epoxidation.
Structure and reactivity of hydroxypropylphosphonic acid epoxidase in fosfomycin biosynthesis by a cation- and flavin-dependent mechanism.,McLuskey K, Cameron S, Hammerschmidt F, Hunter WN Proc Natl Acad Sci U S A. 2005 Oct 4;102(40):14221-6. Epub 2005 Sep 26. PMID:16186494[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
- ↑ 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
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