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Titolo:
CLONING AND FUNCTIONAL EXPRESSION OF THE CDNA-ENCODING RAT LANOSTEROL14-ALPHA DEMETHYLASE
Autore:
SLOANE DL; SO OY; LEUNG R; SCARAFIA LE; SALDOU N; JARNAGIN K; SWINNEY DC;
Indirizzi:
SYNTEX INC,DISCOVERY RES,3401 HILLVIEW AVE S3-1 PALO ALTO CA 94303
Titolo Testata:
Gene
fascicolo: 2, volume: 161, anno: 1995,
pagine: 243 - 248
SICI:
0378-1119(1995)161:2<243:CAFEOT>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
PURIFICATION; GENE; CYTOCHROME-P-450; DEGENERATE; INHIBITION; PRIMERS;
Keywords:
CYTOCHROME P-450; CHOLESTEROL; LIPID-LOWERING DRUG; ATHEROSCLEROSIS;
Tipo documento:
Note
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
22
Recensione:
Indirizzi per estratti:
Citazione:
D.L. Sloane et al., "CLONING AND FUNCTIONAL EXPRESSION OF THE CDNA-ENCODING RAT LANOSTEROL14-ALPHA DEMETHYLASE", Gene, 161(2), 1995, pp. 243-248

Abstract

Lanosterol 14 alpha-demethylase (LDM) is a cytochrome P-450 enzyme inthe biosynthetic pathway of cholesterol. As such, it represents a target for cholesterol-lowering drugs. Rat LDM (rLDM) has been purified from the livers of rats treated with cholestyramine. The purified protein was used to generate tryptic fragments which were then sequenced. The amino acid (aa) sequences were used to design oligodeoxyribonucleotide primers and a DNA fragment was generated by RT-PCR to probe a phagemid library. A clone encoding rLDM was isolated from the livers of cholestyramine-treated rats. The clone contains an open reading frame encoding a polypeptide of 486 aa and a predicted molecular mass of 55 045 Da. The deduced aa sequence shows a high degree of identity to the yeast LDM sequences, as well as sequences which match typical P-450 sequence motifs. When produced in a baculovirus/insect cell culture system, LDM activity was detected and inhibited by the specific inhibitor azalanstat with an IC50 value of less than 2 nM. The isolation of this full-length coding sequence should facilitate research into understanding the direct and indirect effects of LDM in the regulation of cholesterol biosynthesis and the search for cholesterol-lowering drugs.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/11/20 alle ore 06:56:10