Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Allelic variants of human cytochrome P450 1A1 (CYP1A1): effect of T461N and I462V substitutions on steroid hydroxylase specificity
Autore:
Schwarz, D; Kisselev, P; Schunck, WH; Chernogolov, A; Boidol, W; Cascorbi, I; Roots, I;
Indirizzi:
Humboldt Univ, Max Delbruck Ctr Mol Med, Charite, Inst Clin Pharmacol, D-13125 Berlin, Germany Humboldt Univ Berlin Germany D-13125 Pharmacol, D-13125 Berlin, Germany Schering AG, D-1000 Berlin, Germany Schering AG Berlin Germany D-1000Schering AG, D-1000 Berlin, Germany Humboldt Univ, Univ Med Ctr Charite, Inst Clin Pharmacol, Berlin, Germany Humboldt Univ Berlin Germany rite, Inst Clin Pharmacol, Berlin, Germany Acad Sci Belarus, Inst Bioorgan Chem, Minsk, Byelarus Acad Sci Belarus Minsk Byelarus us, Inst Bioorgan Chem, Minsk, Byelarus
Titolo Testata:
PHARMACOGENETICS
fascicolo: 6, volume: 10, anno: 2000,
pagine: 519 - 530
SICI:
0960-314X(200008)10:6<519:AVOHCP>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
CDNA-DIRECTED EXPRESSION; CANCER SUSCEPTIBILITY; LUNG-CANCER; BINDING REGION; POLYMORPHISMS; GENE; IDENTIFICATION; ACID; ACTIVATION; POPULATION;
Keywords:
polymorphism; CYP1A1; hydroxylation; progesterone; testosterone; endogenous substrate;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Schwarz, D Humboldt Univ, Max Delbruck Ctr Mol Med, Charite, Inst Clin Pharmacol, Robert Roessle Str 10, D-13125 Berlin, Germany Humboldt Univ RobertRoessle Str 10 Berlin Germany D-13125 any
Citazione:
D. Schwarz et al., "Allelic variants of human cytochrome P450 1A1 (CYP1A1): effect of T461N and I462V substitutions on steroid hydroxylase specificity", PHARMACOGEN, 10(6), 2000, pp. 519-530

Abstract

Steroid hydroxylation specificities were determined for the wild-type and the two allelic variants of the polymorphic human cytochrome P450 1A1 (CYP1A1) that were associated with amino acid exchanges near the active site of the enzyme, All three variants were expressed in insect cells using recombinant baculoviruses. Each variant protein was spectrally and enzymatically active, as judged by the ability of the prepared microsomes to catalyse O-dealkylation of ethoxyresorufin and pentoxyresorufin in cumene hydroperoxide-mediated reactions, With progesterone and testosterone as substrate, all variants of CYP1A1 exhibited high, but different steroid hydroxylation activities (8-40 pmol hydroxysteroid/min/ pmol CYP1A1, i.e. approximately 800-4000 pmol/min/mg microsomal protein), All three variants exclusively catalysed6 beta-hydroxylation of both steroids, In addition, towards progesterone as substrate, all variants also catalysed 16 alpha-hydroxylations with approximately half of the rate of 6 beta-hydroxylation activity, With progesterone as substrate for 6 beta hydroxylation in 6 beta position, CYP1A1 T461N had the lowest catalytic efficiency (V-max/K-m) followed by the CYP1A1 I462Vvariant and the wild-type enzyme, For 16 alpha-hydroxylation of progesterone, the catalytic efficiencies of the three variants are not statistically significantly different, With testosterone as substrate the CYP1A1 I462V variant catalysed 6 beta-hydroxylation with an efficiency considered not significantly different compared to the wild-type, although both the apparent K-m and V-max were significantly decreased, In contrast, the CYP1A1 T461N variant exhibited significantly decreased catalytic efficiencies compared to both the I462V variant and the wild-type enzyme, These results indicate that all three naturally occurring allelic variants of human CYP1A1 hydroxylate steroid hormones with varying efficiencies in a stereo- and regioselective manner, whereby the CYP1A1 T461N variant exhibited the lowest catalytic efficiency, Pharmacogenetics 10:519-530 (C) 2000 Lippincott Williams & Wilkins.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 01:37:10