Epoxidase

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Revision as of 07:32, 19 June 2024

spinqualitylabelsall models Hydroxypropylphosphonic acid epoxidase complex with fosfomycin, glycerol, NO and Fe+2 ion (PDB code 3scf) Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image Contents 1 Function 2 Relevance 3 Disease 4 Structural highlights 5 3D structures of epoxidase Function Hydroxypropylphosphonic acid epoxidase (HppE) is involved in the biosynthesis of the antibiotic fosfomycin[1]. 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[2]. Squalene epoxidase or squalene monooxygenase is a rate-limiting enzyme in cholesterol biosynthesis[3]. Relevance Fosfomycin is an antibiotic produced by some Streptomyces species. Disease A single mutation in squalene epoxidase causes resistance to terbinafine, the antifungal treatment against dermatophytosis[4]. Structural highlights The . The enzyme uses an induced-fit mechanism to protect high-energy iron-oxygen species formed during catalysis by moving a to seal off the top portion of the active site[5]. . 3D structures of epoxidase Epoxidase 3D structures

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. ↑ 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
5. ↑ 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