Two human liver cDNAs encode UDP-glucuronosyltransferases with 2 log differences in activity toward parallel substrates including hyodeoxycholic acid and certain estrogen derivatives.
Two human liver cDNAs encode UDP-glucuronosyltransferases with 2 log differences in activity toward parallel substrates including hyodeoxycholic acid and certain estrogen derivatives.
复制标题
两种人肝脏 cDNA 编码 UDP-葡萄糖醛酸基转移酶，对平行底物（包括猪去氧胆酸和某些雌激素衍生物）的活性具有 2 个对数差异。
作者：
Joseph K. Ritter;Fan Chen;Y. Sheen;Ronald A. Lubet;Ida S. Owens
两个人肝UDP-葡萄糖醛酸基转移酶cDNA克隆，HLUG 25 [杰克逊，M. R.，等人（1987）Biochem.J.242，581-588]和UDPGTh-2 [Ritter，J.K.，等人（1990）J.Biol.Chem.266，7900-7906]先前已显示编码分别在猪去氧胆酸（HDCA）和某些雌激素衍生物（雌三醇和3，4-儿茶酚雌激素）的葡萄糖醛酸化中有活性的同工酶。在这里，我们报告，UDPGTh-2编码的异构体（udpgth-2）和HLUG 25编码的异构体（udpgth-1）具有平行的糖苷配基特异性。在COS-1细胞中表达后，每种同工酶代谢三种类型的二羟基或三羟基取代的环结构，包括3，4-儿茶酚雌激素（4-羟基雌酮），雌三醇和17-表雌三醇，和HDCA，但udpgth-2同工酶比udpgth-1更有效100倍。udpgth-1和udpgth-2总体上有86%相同（528个氨基酸中有76个差异），其中包括氨基末端前300个氨基酸中的55个差异，该结构域赋予亚型底物特异性。数据表明，在氨基末端的高水平的保守性是不需要的底物选择性的保存。由在其共同限制性位点SacI构建的UDPGTh-1/UDPGTh-2嵌合cDNA编码的葡萄糖醛酸化活性分析（密码子297），NcoI（密码子385），和HhaI（密码子469），表明残基385和469之间的9个氨基酸对于催化效率是重要的，这表明该区域代表了一个对催化作用至关重要但与负责糖苷配基选择的区域不同的结构域。（250字处删节）
Two human liver UDP-glucuronosyltransferase cDNA clones, HLUG25 [Jackson, M. R., et al. (1987) Biochem. J. 242, 581-588] and UDPGTh-2 [Ritter, J. K., et al. (1990) J. Biol. Chem. 266, 7900-7906] have previously been shown to encode isozymes active in the glucuronidation of hyodeoxycholic acid (HDCA) and certain estrogen derivatives (estriols and 3,4-catechol estrogens), respectively. Here we report that the UDPGTh-2-encoded isoform (udpgth-2) and the HLUG25-encoded isoform (udpgth-1) have parallel aglycon specificities. Following expression in COS-1 cells, each isoform metabolized three types of dihydroxy- or trihydroxy-substituted ring structures, including the 3,4-catechol estrogen (4-hydroxyestrone), estriol and 17-epiestriol, and HDCA, but the udpgth-2 isozyme is 100-fold more efficient than udpgth-1. udpgth-1 and udpgth-2 are 86% identical overall (76 differences out of 528 amino acids), including 55 differences in the first 300 amino acids of the amino terminus, a domain which confers isoform substrate specificity. The data indicate that a high level of conservation in the amino terminus is not required for the preservation of substrate selectivity. Analysis of glucuronidation activity encoded by UDPGTh-1/UDPGTh-2 chimeric cDNAs constructed at their common restriction sites, SacI (codon 297), NcoI (codon 385), and HhaI (codon 469), showed that nine amino acids between residues 385 and 469 are important for catalytic efficiency, suggesting that this region represents a domain which is critical for catalysis but distinct from that responsible for aglycon selection.(ABSTRACT TRUNCATED AT 250 WORDS)
影响因子：
56.9
作者：
OREILLY, DR;MILLER, LK
通讯作者：
MILLER, LK
大鼠肝微粒体形成三种类型的 6-羟基胆汁酸葡萄糖苷酸。
影响因子：
6.5
作者：
Zimniak,P;Radominska,A;Zimniak,M;Lester,R
通讯作者：
Lester,R
人肝微粒体雌三醇 UDP 葡萄糖醛酸基转移酶的表征和一级序列。
影响因子：
3.9
作者：
Coffman,BL;Tephly,TR;Irshaid,YM;Green,MD;Smith,C;Jackson,MR;Wooster,R;Burchell,B
通讯作者：
Burchell,B