InterPro domain: IPR018333

Several enzymes catalyse mechanistically related reactions which involve the highly complex cyclic rearrangement of squalene or its 2,3 oxide. Squalene cyclase (SQCY) and 2,3-oxidosqualene cyclase (OSQCY) are integral membrane proteins that catalyse a cationic cyclization cascade converting linear triterpenes to fused ring compounds [ 1 , 2 ]. Lanosterol synthase ( 5.4.99.7 ) (oxidosqualene--lanosterol cyclase) catalyses the cyclization of (S)-2,3-epoxysqualene to lanosterol, the initial precursor of cholesterol, steroid hormones and vitamin D in vertebrates and of ergosterol in fungi (gene ERG7). Cycloartenol synthase ( 5.4.99.8 ) (2,3-epoxysqualene--cycloartenol cyclase), is a plant enzyme that catalyses the cyclization of (S)-2,3-epoxysqualene to cycloartenol [ 3 ], and hopene synthase ( 5.4.99 ) (squalene--hopene cyclase), is a bacterial enzyme that catalyses the cyclization of squalene into hopene or diplopterol, a key step in hopanoid (triterpenoid) metabolism [ 4 , 5 ] also found in Aspergillus fumigatus as part of the gene cluster that mediates the biosynthesis fumihopaside A [ 6 ]. These enzymes are evolutionary related [ 7 ] proteins of about 70 to 85kDa and have an alpha 6 - alpha 6 barrel fold. Deletion of a single glycine residue of Alicyclobacillus acidocaldarius SQCY alters its substrate specificity into that of eukaryotic OSQCY [ 8 ]. Both enzymes have a second minor domain, which forms an alpha-alpha barrel that is inserted into the major domain.

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2. Structure and function of a squalene cyclase. Science 277, 1811-5
3. Isoprenoid biosynthesis: manifold chemistry catalyzed by similar enzymes. Structure 6, 127-33
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7. Isolation of an Arabidopsis thaliana gene encoding cycloartenol synthase by functional expression in a yeast mutant lacking lanosterol synthase by the use of a chromatographic screen. Proc. Natl. Acad. Sci. U.S.A. 90, 11628-32
8. Deletion of the Gly600 residue of Alicyclobacillus acidocaldarius squalene cyclase alters the substrate specificity into that of the eukaryotic-type cyclase specific to (3S)-2,3-oxidosqualene. Angew. Chem. Int. Ed. Engl. 43, 6700-3