Partial purification of 2,3-oxidosqualene-lanosterol cyclase from hog-liver. Evidence for a functional thiol residue

Duriatti, Albert; Schuber, Francis

doi:10.1016/s0006-291x(88)80515-1

Cited by 34 publications

(9 citation statements)

References 15 publications

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“…OSC have been purified and cloned from different species: Candida albicans, Saccharomyces cerevisiae, and Schizosaccharomyces pombe among the fungi; higher plants; the rat; the pig; and human (8)(9)(10)(11)(12)(13)(14)(15)(16)(17). SHC from Alicyclobacillus acidocaldarius has recently been overexpressed in Escherichia coli, purified, and crystallized (18)(19)(20).…”

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confidence: 99%

Conjugated methyl sulfide and phenyl sulfide derivatives of oxidosqualene as inhibitors of oxidosqualene and squalene‐hopene cyclases

Rocco

Bosso

Viola

et al. 2003

Lipids

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Various (1E,3E)- and (1Z,3E)-conjugated methylthio derivatives of oxidosqualene (OS) and conjugated and non-conjugated phenylthio derivatives of OS were obtained. These compounds, designed as inhibitors of pig liver and Saccharomyces cerevisiae 2,3-oxidosqualene-lanosterol cyclases (OSC) (EC 5.4.99.7) and of Alicyclobacillus acidocaldarius squalene-hopene cyclase (SHC) (EC 5.4.99.-), contain the reactive function adjacent to carbons involved in the formation of the third and the fourth cycle during OS cyclization. All the new compounds are inhibitors of OSC and SHC, with various degrees of selectivity. The conjugated methylthio derivatives behaved as potent inhibitors of S. cerevisiae OSC, whereas most of the phenylthio derivatives were especially active toward SHC.

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confidence: 99%

Conjugated methyl sulfide and phenyl sulfide derivatives of oxidosqualene as inhibitors of oxidosqualene and squalene‐hopene cyclases

Rocco

Bosso

Viola

et al. 2003

Lipids

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“…OSCs are membrane-associated enzymes that have been purified and cloned from different species: Candida albicans, Saccharomyces cerevisiae, Schizosaccharomyces pombe among the fungi; higher plants, the rat, the pig and man. [1][2][3][4][5][6][7][8][9][10][11][12] The predicted molecular masses range from 80 to 90 kDa and the amino acid sequences determined show significant homology between rat, yeast and plant enzymes. Sequence comparison of OSCs with bacterial squalene hopene cyclase 13 show 17-27% homogeneity and reveals the existence of a highly conserved repetitive motif (the QW motif ) rich in aromatic amino acids.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of (E)- and (Z)-29-methylidyne-2,3-oxidosqualene derivatives as inhibitors of liver and yeast oxidosqualene cyclase

Ceruti

Viola

Balliano

et al. 2002

J. Chem. Soc., Perkin Trans. 1

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The synthesis of (E )-and (Z )-29-methylidyne-2,3-oxidosqualene derivatives is described starting from the C 22 and C 17 squalene aldehyde monobromohydrins. The conversion was achieved by means of a Wittig reaction, followed by desilylation of the terminal acetylene. For trisubstituted 1,3-enynes, preliminary alkylation with a suitable allyl bromide was performed. A new procedure for the synthesis of squalene aldehyde C 27 , C 22 and C 17 monobromohydrins is also described. Some of the new compounds behaved as inhibitors of pig liver and yeast oxidosqualene cyclase and were time-dependent inhibitors of the animal enzyme.

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“…Furthermore, there are six conserved Cys (C-282, C-457, C-534, C-585, C-617, C-701, one at the 29-MOS binding site), and four conserved His (H-145, H-226, H-233, H-290) residues. The presence of an essential cysteinyl group in the active site of the enzyme has been previously suggested, since the OSC activity can be efficiently inhibited by SH reagents such as p-chloromercuribenzenesulfonic acid and Nethylmaleimide (13,42,43). In contrast, diethyl pyrocarbonate, a histidyl-selective reagent, does not inhibit OSC activity (42,43).…”

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confidence: 99%

“…The presence of an essential cysteinyl group in the active site of the enzyme has been previously suggested, since the OSC activity can be efficiently inhibited by SH reagents such as p-chloromercuribenzenesulfonic acid and Nethylmaleimide (13,42,43). In contrast, diethyl pyrocarbonate, a histidyl-selective reagent, does not inhibit OSC activity (42,43). Finally, a disproportionately higher number of Gly (29 of 59 residues} and Pro (11 of 38 residues) are also conserved, suggesting important conserved elements of secondary structure.…”

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confidence: 99%

Molecular cloning, characterization, and functional expression of rat oxidosqualene cyclase cDNA.

Abe

Prestwich

1995

Proc. Natl. Acad. Sci. U.S.A.

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A cDNA encoding rat oxidosqualene lanosterol-cyclase [lanosterol synthase; (S)-2,3-epoxysqualene mutase (cyclizing, lanosterol- Oxidosqualene lanosterol-cyclase (OSC) [lanosterol synthase; (S)-2,3-epoxysqualene mutase (cyclizing, lanosterol-forming), EC 5.4.99.7] catalyzes the conversion of (3S)-2,3-oxidosqualene to lanosterol, forming a total of six new carbon-carbon bonds in a single reaction (1). The regulation of OSC levels in vivo has clinical importance and has been a potential target for the design of hypercholesteremic drugs (2). The formation of lanosterol is initiated in the chair-boat-chair-like conformation of oxidosqualene, and the proton-initiated cyclization is postulated to proceed through a series of rigidly held carbocationic intermediates (1). The intermediate C-20 protosterol cation then undergoes backbone rearrangement to yield the lanosterol skeleton ( Fig. 1) (3-6). Oxidosqualene is also the precursor for a variety of other polycyclic triterpenes, and the relationship between enzyme structure and cyclization mechanism has been extensively studied (1).Several OSCs have been purified to homogeneity from vertebrate (7-9), plant (10-13), and yeast sources (14). Re

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Partial purification of 2,3-oxidosqualene-lanosterol cyclase from hog-liver. Evidence for a functional thiol residue

Cited by 34 publications

References 15 publications

Conjugated methyl sulfide and phenyl sulfide derivatives of oxidosqualene as inhibitors of oxidosqualene and squalene‐hopene cyclases

Conjugated methyl sulfide and phenyl sulfide derivatives of oxidosqualene as inhibitors of oxidosqualene and squalene‐hopene cyclases

Synthesis of (E)- and (Z)-29-methylidyne-2,3-oxidosqualene derivatives as inhibitors of liver and yeast oxidosqualene cyclase

Molecular cloning, characterization, and functional expression of rat oxidosqualene cyclase cDNA.

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