Umbenhauer D R, Martin M V, Lloyd R S, Guengerich F P
Biochemistry. 1987 Feb 24;26(4):1094-9. doi: 10.1021/bi00378a016.
A cDNA sequence related to the human cytochrome P-450 responsible for S-mephenytoin 4-hydroxylation (P-450MP) has been isolated from a human liver bacteriophage lambda gt11 library with antibodies specific for P-450MP. The total length of the cDNA is 2.5 kilobases (kb), of which there is a 1.6-kb EcoRI fragment coding for all but five amino acids corresponding to the N-terminus of the protein and including a small noncoding region at the 3' end. This 1.6-kb fragment has been sequenced and used as a probe to analyze human genomic DNA and liver RNA. The sequence shows extensive sequence similarity with that of rabbit liver cytochrome P-450 progesterone 21-hydroxylase [Tukey, R. H., Okino, S., Barnes, H., Griffin, K. J., & Johnson, E. F. (1985) J. Biol. Chem. 260, 13347-13354], and this cDNA, like the rabbit clone, appears to be part of a multigene family. At least two liver mRNA species, 2.2 kb and 3.5 kb, hybridize to the cDNA sequence. The cloning of this gene should aid in analyzing the molecular basis for the genetic polymorphism of S-mephenytoin 4-hydroxylation reported in humans.
利用对人细胞色素P - 450MP具有特异性的抗体，从人肝脏噬菌体λgt11文库中分离出了一段与人细胞色素P - 450相关的cDNA序列，该细胞色素P - 450负责S - 美芬妥因4 - 羟化作用（P - 450MP）。cDNA的总长度为2.5千碱基（kb），其中有一个1.6 kb的EcoRI片段，编码除了与该蛋白质N端相对应的五个氨基酸以外的所有氨基酸，并且在3'端包括一个小的非编码区。对这个1.6 kb的片段进行了测序，并将其用作探针来分析人基因组DNA和肝脏RNA。该序列与兔肝脏细胞色素P - 450孕酮21 - 羟化酶的序列显示出广泛的序列相似性[图基，R. H.，冲野，S.，巴恩斯，H.，格里芬，K. J.，& 约翰逊，E. F.（1985年）《生物化学杂志》260，13347 - 13354]，并且这个cDNA，与兔克隆一样，似乎是一个多基因家族的一部分。至少有两种肝脏mRNA种类，2.2 kb和3.5 kb，与该cDNA序列杂交。这个基因的克隆应该有助于分析人类中报道的S - 美芬妥因4 - 羟化作用遗传多态性的分子基础。
