This entry represents the N-terminal domain of squalene cyclases [1, 2].

Several enzymes catalyse mechanistically related reactions which involvethe 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 catalyze a cationic cyclization cascade converting linear triterpenes to fused ring compounds [3, 4]. 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 catalyzes the cyclization of (S)-2,3-epoxysqualene to cycloartenol [5], and hopene synthase (5.4.99) (squalene--hopene cyclase), is a bacterial enzyme that catalyzes the cyclization of squalene into hopene or diplopterol, a key step in hopanoid (triterpenoid) metabolism [6, 6]. These enzymes are evolutionary related [7] proteins of about 70 to 85 kDa 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.

1. The structure of the membrane protein squalene-hopene cyclase at 2.0 A resolution. J. Mol. Biol. 286, 175-87
2. Binding structures and potencies of oxidosqualene cyclase inhibitors with the homologous squalene-hopene cyclase. J. Med. Chem. 46, 2083-92
3. Enzyme Mechanisms for Polycyclic Triterpene Formation. Angew. Chem. Int. Ed. Engl. 39, 2812-2833
4. Structure and function of a squalene cyclase. Science 277, 1811-5
5. Isoprenoid biosynthesis: manifold chemistry catalyzed by similar enzymes. Structure 6, 127-33
6. Properties of purified squalene-hopene cyclase from Bacillus acidocaldarius. Eur. J. Biochem. 194, 75-80
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

This entry represents the N-terminal domain of squalene cyclases [1,
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