cDNA cloning and sequence and cDNA-directed expression of human P450 IIB1: identification of a normal and two variant cDNAs derived from the CYP2B locus on chromosome 19 and differential expression of the IIB mRNAs in human liver.
cDNA cloning and sequence and cDNA-directed expression of human P450 IIB1: identification of a normal and two variant cDNAs derived from the CYP2B locus on chromosome 19 and differential expression of the IIB mRNAs in human liver.
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人 P450 IIB1 的 cDNA 克隆和序列以及 cDNA 定向表达：鉴定源自 19 号染色体上 CYP2B 基因座的正常和两个变异 cDNA，以及人肝脏中 IIB mRNA 的差异表达。
DOI：
10.1021/bi00444a029
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发表时间：
1989
期刊：
影响因子：
2.9
通讯作者：
F. J. Gonzalez
中科院分区：
文献类型：
--
作者：
Shigeru Yamano;Patson T. Nhamburo;T. Aoyama;U. Meyer;Tadanobu Inaba;Werner Kalow;H. Gelboin;O. McBride;F. J. Gonzalez
以大鼠IIB1 cDNA为探针，从人肝脏lambda gt11文库中分离到IIB基因家族P450的完整编码序列，命名为hIIB1。从cDNA序列中推断出hIIB1蛋白含有491个氨基酸，计算分子量为56,286，与大鼠IIB1蛋白氨基酸相似性为76%。利用牛痘病毒系统表达该cDNA，得到了co结合谱谱降低的P450，最大吸收为452nm。所表达的人酶能够催化7-乙氧基香豆素的去乙基化。检测13个肝脏的总RNA，检测hIIB mRNA水平。两个肝脏的mRNA水平很高，四个肝脏的mRNA水平中等，八个肝脏的mRNA水平很低，或者没有检测到。这些数据表明，hIIB1基因在人类中存在缺陷，或者hIIB1基因在我们的肝脏标本中受到调节和可变诱导。为了寻找突变mRNA转录本，我们从表达低水平hIIB1 mRNA的肝脏中构建了文库。分离到的hIIB2 cDNA与hIIB1 cDNA完全相同，除了在其5'端附近存在一个与假定的外显子4相对应的不寻常的DNA改变。这种改变是由缺失29 bp和插入44 bp的非同源DNA引起的。这种序列替换发生在第三和第四外显子的连接处，正如从大鼠IIB1基因的结构预测的那样，这表明错误的剪接可能导致了hIIb2转录物的变异。（摘要删节250字）
A cDNA designated hIIB1, representing the entire coding sequence of a P450 in the IIB gene family, was isolated from a human liver lambda gt11 library by using the rat IIB1 cDNA as a probe. The hIIB1 protein, deduced from the cDNA sequence, contained 491 amino acids, had a calculated molecular weight of 56,286, and displayed 76% amino acid similarity with the rat IIB1 protein. Expression of this cDNA, using the vaccinia virus system, yielded a P450 that had a reduced CO-binding spectrum with an absorption maximum of 452 nm. The expressed human enzyme was able to catalyze the deethylation of 7-ethoxy-coumarin. Total RNA from 13 livers was probed for levels of hIIB mRNA. Two livers had high levels, four contained moderate levels, and eight contained very low, or no detectable, mRNA. These data suggest either that defective hIIB1 genes exist in humans or that the hIIB1 gene is regulated and variably induced in our liver specimens. To search for mutant mRNA transcripts, libraries were constructed from livers expressing low levels of hIIB1 mRNA. A cDNA, designated hIIB2, was isolated that was identical with the hIIB1 cDNA except for the presence of an unusual alteration of the DNA near its 5' end corresponding to the putative exon 4. This alteration was caused by a deletion of 29 bp and an insertion of 44 bp of nonhomologous DNA. This sequence replacement occurs at the junction of the third and fourth exons as predicted from the structure of the rat IIB1 gene, suggesting that a faulty splice might have given rise to the variant hIIb2 transcript.(ABSTRACT TRUNCATED AT 250 WORDS)
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DOI：
--
发表时间：
1986-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
T. Shimada;K. Misono;F. Guengerich
通讯作者：
T. Shimada;K. Misono;F. Guengerich
人肝细胞色素 P-450 的纯化和表征，该细胞色素参与异喹啉 4-羟基化和非那西丁 O-去乙基化，这是氧化药物代谢中遗传多态性的两个原型。
DOI：
--
发表时间：
1985
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Distlerath,LM;Reilly,PE;Martin,MV;Davis,GG;Wilkinson,GR;Guengerich,FP
通讯作者：
Guengerich,FP
DOI：
10.1073/pnas.82.4.1074
发表时间：
1985-01-01
影响因子：
11.1
作者：
TABOR, S;RICHARDSON, CC
通讯作者：
RICHARDSON, CC
影响因子：
5.6
作者：
DEININGER, PL;JOLLY, DJ;SCHMID, CW
通讯作者：
SCHMID, CW
人细胞色素 P-450 4 mRNA 和基因：其 mRNA 中含有 Alu 序列的多基因家族的一部分。
DOI：
10.1073/pnas.83.18.6731
发表时间：
1986
影响因子：
11.1
作者：
Quattrochi,LC;Pendurthi,UR;Okino,ST;Potenza,C;Tukey,RH
通讯作者：
Tukey,RH