Showing papers on "Lanosterol synthase published in 1996"
TL;DR: All of the resultant mutant enzymes retained the ability to complement the Sc.
70 citations
TL;DR: In this article, it was shown that the six-membered C-ring of sterols is formed via a five-modal predecessor, which was in accord with expectations based on previous work.
41 citations
TL;DR: The relatively modest potency of inhibition of lanosterol synthase by the tetracyclic ammonium ion 10, a structural analog of the protosterol cation 4, IC50 = 22 μM, indicates that the proton-proton cation is not strongly bound by the enzyme.
20 citations
TL;DR: These compounds are electron-poor aromatic mimics of a monocyclized transition state or high-energy intermediate formed from oxidosqualene, which may explain their selective action in Candida albicans.
Abstract: The N-(4E,8E)-5,9,13-trimethyl-4,8,12-tetradecatrien-1- ylpyridinium and N-(4E,8E)-5,9,13-trimethyl-4,8,12-tetradecatrien-1- ylpicolinium cations were evaluated for their ability to inhibit 2,3-oxidosqualene-lanosterol cyclase activity in Candida albicans. Both compounds inhibited fungal growth, were fungicidal, and resulted in the accumulation of squalene epoxide concurrent with a decrease in ergosterol, monomethyl sterols, and lanosterol, as was expected for the specific inhibition of 2,3-oxidosqualene-lanosterol cyclase activity. These compounds are electron-poor aromatic mimics of a monocyclized transition state or high-energy intermediate formed from oxidosqualene, which may explain their selective action.
18 citations
TL;DR: A portion of the human lanosterol synthase cDNA was cloned from a brain cDNA library and determined its nucleotide sequence and the predicted human protein shows 83% identity to its rat and 40% to its yeast homolog.
Abstract: In order to contribute to the development of the transcriptional map of human chromosome 21 (HC21) we have used exon trapping to identify portions of HC21 genes. Using pools of random HC21-specific cosmids from the LL21NC02-Q library and cosmids from 21q22.3 we have identified five different coding regions with strong homology to the lanosterol synthase genes of rat and yeast. This enzyme catalyzes the cyclization of squalene-2,3-epoxide lanosterol, which is the parental compound of all steroids in mammals. Using somatic cell hybrids and HC21 yeast artificial chromosomes (YACS) and cosmids, we mapped the human lanosterol synthase cDNA gene to 2lq22.3 between markers D21S25 and 21qter. Cosmid Q7G8 from the LL21NC02-Q library and YAC 145D8 from the CEPH HC21 contig contain this human gene. We cloned a portion of the human lanosterol synthase cDNA (almost 85% of the coding region) from a brain cDNA library and determined its nucleotide sequence. The predicted human protein shows 83% identity to its rat and 40% to its yeast homolog. No obvious candidate human disease exists for lanosterol synthase deficiency and the role (if any) of triplication of this gene in the various phenotypes of trisomy 21 is unknown.
17 citations