2,3-Oxidosqualene cyclase

Fig. 5.1 Cyclization of 2,3-oxidosqualene to sterols and triterpenoids. The 2,3-oxidosqualene cyclase enzymes that catalyse the formation of the different products are indicated LS, lanosterol synthase CS, cycloartenol synthase LuS, lupeol synthase PAS, P-amyrin synthase aAS, a-amyrin synthase.

Characterization of fi-Amyrin Synthase from Avena strigosa-A Novel Oxidosqualene Cyclase... 

KUSHIRO, T., SHIBUYA, M., EBIZUKA, Y P-Amyrin synthase. Cloning of oxidosqualene cyclase that catalyzes the formation of the most popular triterpene among higher plants, Eur. J. Biochem., 1998,256,238-244. 

MATSUDA, S.P.T., On the diversity of oxidosqualene cyclases. In Biochemical Principles and Mechanisms of Biosynthesis and Degradation of Polymers (A. Steinbuchel, ed,), Wiley-VCH, Weinheim. 1998, pp. 300-307. 

CATTEL, L., CERUTI, M., 2,3-Oxidosqualene cyclase and squalene epoxidase Enzymology, mechanism and inhibitors. In Physiology and Biochemistry of Sterols (G.W. Patterson and W.D. Nes, eds,), American Oil Chemists Society, Champaign. 1992, pp. 50-82. 

HARALAMPIDIS, K, BRYAN, G Qi, X., PAPADOPOULOU, K., BAKHT, S, MELTON, R, OSBOURN, A.E., A new class of oxidosqualene cyclases directs synthesis of antimicrobial phytoprotectants in monocots, Proc. Natl. Acad. Sci., USA, 2001,98,13431-13436. 

PORALLA, K HEWELT, A., PRESTWICH, G.D., ABE, I., REIPEN, I., SPRENGER, G., A specific amino acid repeat in squalene and oxidosqualene cyclases, TIBS, 1994, 19,157-158. 

FANG, T-Y., BAISTED, D.J., 2,3-Oxidosqualene cyclase and cycloartenol-S-adenosylmethionine methyltransferase activitites in vivo in the cotyledon and axis tissues of germinating pea seeds, Biochem. J., 1975,150, 323-328. 

Keywords. Saponins, Triterpenoids, Sterols, 2,3-Oxidosqualene cyclases, Glycosyltransferases... 

Table 2. 2,3-Oxidosqualene cyclases that have been cloned and their function confirmed by expression in yeast ...

The activity of 2,3-oxidosqualene cyclases is associated with microsomes, indicating their membrane-bound nature. However, the predicted amino acid sequences of these enzymes generally lack signal sequences and obvious transmembrane domains. Addition of hydrophobic membrane-localising regions to OSCs during evolution may have removed selection pressures that maintained alternate mechanisms for membrane localisation [33]. Consistent with this, there is a non-polar plateau on the surface of the A. acidocaldarius SC enzyme which is believed to be immersed in the centre of the membrane. The squalene substrate for SC is likely to diffuse from the membrane interior into the central cavity of the enzyme via this contact region [55,56]. 

Table 3. Conserved amino acid motifs of 2,3-oxidosqualene cyclases...

Kushiro T, Shibuya M, Ebizuka Y (1998) Molecular cloning of oxidosqualene cyclase cDNA from Panax ginseng the isogene that encodes /3-amyrin synthase. In Ageta H, Aimi N, Ebizuka Y, Pujita T, Honda G (eds) Towards natural medicine research in the 21 st century. Elsevier Science, Amsterdam, p 421... 

Cattel L, Ceruti M (1992) 2,3-Oxidosqualene cyclase and squalene epoxidase enzymology,... 

Hasserodt, J., Janda, K.D., and Lerner, R.A. (2000) Anibodies mimic natural oxidosqualene-cyclase action in steroid ring A formation, J. Am. Chem. Soc. 122, 40-45. 

Xiao, X.-y., and Prestwich, G.D. (1991). 24-Methylidene-2,3-oxidosqualene a potent mechanism-based inactivator of oxidosqualene cyclase. 7 Am Chem Soc 113 9673-9674. 

The racemic [21- " C]oxidosqualene analogue (1), which has an 18Z instead of the normal 8E double bond, was converted by 2,3-oxidosqualene cyclase into the norlanosterol derivative (2) with the unnatural (205) configuration.This result is readily interpreted in terms of the Cornforth proposal of attachment, and subsequent elimination, of the enzyme or an exogenous nucleophile to C-20 during the initial cyclization. The syntheses of (1) and authentic samples of the (205)- and (20i )-norlanosterol derivatives have been described. ... 

Figure 26.12. Oxidosqualene Cyclase. The structure of an enzyme homologous to oxidosqualene cyclase shows a...

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