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Titolo:
Characterization of a novel variant (S145C/L311V) of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase in human liver
Autore:
Kume, T; Iwasa, H; Shiraishi, H; Yokoi, T; Nagashima, K; Otsuka, M; Terada, T; Takagi, T; Hara, A; Kamataki, T;
Indirizzi:
Tanabe Seiyaku Co Ltd, Discovery Res Lab, Toda, Saitama 3358505, Japan Tanabe Seiyaku Co Ltd Toda Saitama Japan 3358505 , Saitama 3358505, Japan Hokkaido Univ, Grad Sch Pharmaceut Sci, Lab Drug Metab, Sapporo, Hokkaido,Japan Hokkaido Univ Sapporo Hokkaido Japan Drug Metab, Sapporo, Hokkaido,Japan Gifu Pharmaceut Univ, Biochem Lab, Gifu, Japan Gifu Pharmaceut Univ GifuJapan armaceut Univ, Biochem Lab, Gifu, Japan Hokkaido Univ Hosp, Dept Pathol, Sapporo, Hokkaido 060, Japan Hokkaido Univ Hosp Sapporo Hokkaido Japan 060 apporo, Hokkaido 060, Japan Osaka Univ, Fac Pharmaceut Sci, Biochem Lab, Osaka, Japan Osaka Univ Osaka Japan v, Fac Pharmaceut Sci, Biochem Lab, Osaka, Japan Osaka Univ, Genome Informat Res Ctr, Osaka, Japan Osaka Univ Osaka Japan saka Univ, Genome Informat Res Ctr, Osaka, Japan
Titolo Testata:
PHARMACOGENETICS
fascicolo: 6, volume: 9, anno: 1999,
pagine: 763 - 771
SICI:
0960-314X(199912)9:6<763:COANV(>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
KETO REDUCTASE SUPERFAMILY; DIHYDRODIOL DEHYDROGENASE; CHLORDECONE REDUCTASE; CARBONYL REDUCTASE; ALDEHYDE REDUCTASE; MULTIPLE FORMS; RABBIT LIVER; PURIFICATION; PROTEINS; RAT;
Keywords:
polymorphism; aldo-keto reductase family; ketone-containing xenobiotics;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
40
Recensione:
Indirizzi per estratti:
Indirizzo: Kume, T Tanabe Seiyaku Co Ltd, Discovery Res Lab, Toda, Saitama 3358505, Japan Tanabe Seiyaku Co Ltd Toda Saitama Japan 3358505 a 3358505, Japan
Citazione:
T. Kume et al., "Characterization of a novel variant (S145C/L311V) of 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase in human liver", PHARMACOGEN, 9(6), 1999, pp. 763-771

Abstract

Human liver 3 alpha-hydroxysteroid/dihydrodiol dehydrogenase (DD) is involved in the metabolism of steroid hormones and polycyclic aromatic hydrocarbons, and is also responsible for the reduction of ketone-containing drugs. To account for the interindividual difference in the activity, we isolated and characterized clones for the human liver enzymes, The sequence of the cDNA clone coding for the variant differed from that coding for the wild-type DD by two nucleotides (substitutions of C with G at positions 434 and 931) which caused two amino acid replacements, Ser(145) to Cys (S145C) and Leu(311) to Val (L311V), The heterologous expression of the variant mRNA was confirmed in four of 31 liver samples from Japanese by an allele-specific polymerase chain reaction, The effects of the mutations on the catalytic properties were examined with the recombinant enzymes expressed in Escherichia coli. The introduction of S145C/L311V double mutations resulted in three- to five-fold decreased activities for xenobiotic and steroidal substrates, whereas no significant change was observed by an introduction of the S145C mutation alone, The results substantiate the existence of polymorphic forms for human liver DD, and also suggest the importance of the residue at position 311 for substrate binding to the enzyme, Pharmacogenetics 9:763-771 (C)1999 Lippincott Williams & Wilkins.

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Documento generato il 25/01/20 alle ore 03:27:03