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Titolo:
CLONING AND EXPRESSION OF CYP2F3, A CYTOCHROME-P450 THAT BIOACTIVATESTHE SELECTIVE PNEUMOTOXINS 3-METHYLINDOLE AND NAPHTHALENE
Autore:
WANG HF; LANZA DL; YOST GS;
Indirizzi:
UNIV UTAH,DEPT PHARMACOL & TOXICOL,112 SKAGGS HALL SALT LAKE CITY UT 84112 UNIV UTAH,DEPT PHARMACOL & TOXICOL SALT LAKE CITY UT 84112
Titolo Testata:
Archives of biochemistry and biophysics
fascicolo: 2, volume: 349, anno: 1998,
pagine: 329 - 340
SICI:
0003-9861(1998)349:2<329:CAEOCA>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
SUBSTRATE RECOGNITION SITES; CDNA-DIRECTED EXPRESSION; ESCHERICHIA-COLI; CATALYTIC PROPERTIES; SPECTRAL CHARACTERIZATION; PURIFICATION; RECONSTITUTION; PULMONARY; GENE; ACID;
Keywords:
CYTOCHROME P450, CYP2F3; CLONING; EXPRESSION; 3-METHYLINDOLE; REACTIVE INTERMEDIATE; PNEUMOTOXIN; BIOACTIVATION; DEHYDROGENATION; 3-METHYLENEINDOLENINE; NAPHTHALENE; NAPHTHALENE 1R,2S-OXIDE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
55
Recensione:
Indirizzi per estratti:
Citazione:
H.F. Wang et al., "CLONING AND EXPRESSION OF CYP2F3, A CYTOCHROME-P450 THAT BIOACTIVATESTHE SELECTIVE PNEUMOTOXINS 3-METHYLINDOLE AND NAPHTHALENE", Archives of biochemistry and biophysics, 349(2), 1998, pp. 329-340

Abstract

Members of the CYP2F gene subfamily are selectively expressed in lungtissues and have been implicated as important catalysts in the formation of reactive intermediates from several pneumotoxic chemicals, Human CYP2F1 bioactivates 3-methylindole (3MI), while mouse CYP2F2 bioactivates naphthalene. Although 3MI is a potent pneumotoxin in ruminants and rodents, the participation of cytochrome P450s from the 2F subfamily in 3MI bioactivation has not been fully defined, To test the hypothesis that a goat lung 2F homologue uniquely catalyzes the dehydrogenation of 3MI to the putative electrophile S-methyleneindolenine, the CYP2F3 cDNA was cloned from a goat lung cDNA library and expressed in Escherichia coli, The predicted amino acid sequence of CYP2F3 possessed 82% identity to both human CYP2F1 and mouse CYP2F2, CYP2F3 was mutated at the 5' end, expressed in E. coli, and shown to have a molecular massof 50 kDa. The reconstituted enzyme uniquely catalyzed only the dehydrogenation of 3MI to form 3-methyleneindolenine, an electrophilic intermediate, without detectable formation of other products, thus demonstrating highly unusual selectivity for dehydrogenation rather than hydroxylation of a substrate, Immunoinhibition studies demonstrated that about 20% of the production of the intermediate in goat lung microsomalsamples was produced by CYP2F3, The CYP2F3 enzyme had a specific activity that was similar to that of human cDNA-expressed CYP2F1. CYP2F3 also stereoselectively catalyzed the formation of the 1R,2S-oxide from naphthalene; this stereoisomer is the putative pneumotoxin, The enzyme, however, lacked catalytic activity with other common P450 substratesincluding 7-ethoxycoumarin, a substrate for CYP2F1, indicating that the substrate selectivity of CYP2F3 appears to be high. (C) 1998 Academic Press.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/04/20 alle ore 12:10:56