Epoxidase

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<StructureSection load='3scf' size='340' side='right' caption='Hydroxypropylphosphonic acid epoxidase complex with fosfomycin, glycerol, NO and Fe+2 ion (PDB code [[3scf]])' scene=''>
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<StructureSection load='3scf' size='350' side='right' caption='Hydroxypropylphosphonic acid epoxidase complex with fosfomycin, glycerol, NO and Fe+2 ion (PDB code [[3scf]])' scene='' pspeed='8'>
== Function ==
== Function ==
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'''Hydroxypropylphosphonic acid epoxidase''' (HppE) is involved in the biosynthesis of the antibiotic fosfomycin<ref>PMID:16186494</ref>. HppE is a Zn+2/Fe+2-dependent enzyme. '''Halohydrin epoxidase''' (HHE) is involved in the degradation of halohydrins by the displacement of a halogen in halohydrins to produce the epoxide<ref>PMID:26422370</ref>.
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'''Hydroxypropylphosphonic acid epoxidase''' (HppE) is involved in the biosynthesis of the antibiotic fosfomycin<ref>PMID:16186494</ref>. HppE is a Zn+2/Fe+2-dependent enzyme.
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*'''Halohydrin epoxidase''' (HHE) is involved in the degradation of halohydrins by the displacement of a halogen in halohydrins to produce the epoxide<ref>PMID:26422370</ref>.
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*'''Squalene epoxidase''' or '''squalene monooxygenase''' is a rate-limiting enzyme in cholesterol biosynthesis<ref>PMID:30792392</ref>.
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*'''1,2-phenylacetyl-CoA epoxidase''' is part of the catabolic pathway of Phe and phenylacetate<ref>PMID:20660314</ref>.
== Relevance ==
== Relevance ==
Fosfomycin is an antibiotic produced by some ''Streptomyces'' species.
Fosfomycin is an antibiotic produced by some ''Streptomyces'' species.
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== Disease ==
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A single mutation in '''squalene epoxidase''' causes resistance to terbinafine, the antifungal treatment against dermatophytosis<ref>PMID:37236595</ref>.
== Structural highlights ==
== Structural highlights ==
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The active site of HppE contains fosfomycin and Fe+2. The enzyme uses an induced-fit mechanism to protect high-energy iron-oxygen species formed during catalysis by moving a β-hairpin termed cantilever to seal off the top portion of the active site<ref>PMID:21682308</ref>..
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The <scene name='75/752206/Cv/6'>active site of HppE contains fosfomycin and Fe+2</scene>. The enzyme uses an induced-fit mechanism to protect high-energy iron-oxygen species formed during catalysis by moving a <scene name='75/752206/Cv/7'>β-hairpin termed cantilever</scene> to seal off the top portion of the active site<ref>PMID:21682308</ref>. <scene name='75/752206/Cv/8'>Fe coordination site</scene>.
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</StructureSection>
 
==3D structures of epoxidase==
==3D structures of epoxidase==
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[[Epoxidase 3D structures]]
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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</StructureSection>
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{{#tree:id=OrganizedByTopic|openlevels=0|
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* 2-hydroxypropylphosphonic acid epoxidase
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**[[5u55]], [[5u5d]] – PsPsf4 + Mn + fosfomycin – ''Pseudomonas syringae''<br />
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**[[5u57]], [[5u58]] – PsPsf4 + Fe + fosfomycin <br />
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**[[4j1w]], [[4j1x]], [[3scf]], [[3scg]] – SwHppE + Fe + fosfomycin – ''Strepomyces wedmorensis'' <br />
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**[[1zz6]] – SwHppE <br />
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**[[2bnm]] – SwHppE + Zn <br />
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**[[1zz9]] – SwHppE + Fe <br />
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**[[1zzc]] – SwHppE + Co <br />
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**[[1zz7]], [[1zz8]] – SwHppE + Fe + fosfomycin <br />
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**[[3sch]], [[1zzb]] – SwHppE + Co + fosfomycin <br />
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**[[2bnn]], [[2bno]] – SwHppE + Zn + fosfomycin <br />
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* Halohydrin epoxidase
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**[[5b12]] – CoHHE B (mutant) - ''Corynebacterium'' <br />
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**[[4zd9]], [[4zu3]] – CoHHE B <br />
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**[[4z9f]] – CoHHE A (mutant) <br />
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* P450 epoxidase see [[Cytochrome P450]]
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}}
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== References ==
== References ==
<references/>
<references/>
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[[Category:Topic Page]]

Current revision

Hydroxypropylphosphonic acid epoxidase complex with fosfomycin, glycerol, NO and Fe+2 ion (PDB code 3scf)

Drag the structure with the mouse to rotate

References

  1. ↑ 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
  2. ↑ Watanabe F, Yu F, Ohtaki A, Yamanaka Y, Noguchi K, Yohda M, Odaka M. Crystal structures of halohydrin hydrogen-halide-lyases from Corynebacterium sp. N-1074. Proteins. 2015 Dec;83(12):2230-9. doi: 10.1002/prot.24938. Epub 2015 Oct 16. PMID:26422370 doi:http://dx.doi.org/10.1002/prot.24938
  3. ↑ Brown AJ, Chua NK, Yan N. The shape of human squalene epoxidase expands the arsenal against cancer. Nat Commun. 2019 Feb 21;10(1):888. PMID:30792392 doi:10.1038/s41467-019-08866-y
  4. ↑ Teufel R, Mascaraque V, Ismail W, Voss M, Perera J, Eisenreich W, Haehnel W, Fuchs G. Bacterial phenylalanine and phenylacetate catabolic pathway revealed. Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14390-5. doi:, 10.1073/pnas.1005399107. Epub 2010 Jul 21. PMID:20660314 doi:10.1073/pnas.1005399107
  5. ↑ Gupta AK, Cooper EA, Wang T, Polla Ravi S, Lincoln SA, Piguet V, McCarthy LR, Bakotic WL. Detection of Squalene Epoxidase Mutations in United States Patients with Onychomycosis: Implications for Management. J Invest Dermatol. 2023 Dec;143(12):2476-2483.e7. PMID:37236595 doi:10.1016/j.jid.2023.04.032
  6. ↑ Yun D, Dey M, Higgins LJ, Yan F, Liu HW, Drennan CL. Structural Basis of Regiospecificity of a Mononuclear Iron Enzyme in Antibiotic Fosfomycin Biosynthesis. J Am Chem Soc. 2011 Jun 30. PMID:21682308 doi:10.1021/ja2025728

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Michal Harel, Alexander Berchansky

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