Inter-isoform Hetero-dimerization of Human UDP-Glucuronosyltransferases (UGTs) 1A1, 1A9, and 2B7 and Impacts on Glucuronidation Activity.
Inter-isoform Hetero-dimerization of Human UDP-Glucuronosyltransferases (UGTs) 1A1, 1A9, and 2B7 and Impacts on Glucuronidation Activity.
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人 UDP-葡萄糖醛酸基转移酶 (UGT) 1A1、1A9 和 2B7 的异构体间异二聚化及其对葡萄糖醛酸化活性的影响
DOI：
10.1038/srep34450
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发表时间：
2016-11-18
影响因子：
4.6
通讯作者：
Zeng S
中科院分区：
文献类型：
--
作者：
Yuan LM;Gao ZZ;Sun HY;Qian SN;Xiao YS;Sun LL;Zeng S
Human UDP-glucuronosyltransferases (UGTs) play a pivotal role in phase II metabolism by catalyzing the glucuronidation of endobiotics and xenobiotics. The catalytic activities of UGTs are highly impacted by both genetic polymorphisms and oligomerization. The present study aimed to assess the inter-isoform hetero-dimerization of UGT1A1, 1A9, and 2B7, including the wild type (1A1*1, 1A9*1, and 2B7*1) and the naturally occurring (1A1*1b, 1A9*2/*3/*5, and 2B7*71S/*2/*5) variants. The related enzymes were double expressed in Bac-to-Bac systems. The fluorescence resonance energy transfer (FRET) technique and co-immunoprecipitation (Co-IP) revealed stable hetero-dimerization of UGT1A1, 1A9, and 2B7 allozymes. Variable FRET efficiencies and donor-acceptor distances suggested that genetic polymorphisms resulted in altered affinities to the target protein. In addition, the metabolic activities of UGTs were differentially altered upon hetero-dimerization via double expression systems. Moreover, protein interactions also changed the regioselectivity of UGT1A9 for querectin glucuronidation. These findings provide in-depth understanding of human UGT dimerization as well as clues for complicated UGT dependent metabolism in humans.
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影响因子：
2.1
作者：
Fujiwara, Ryoichi;Itoh, Tomoo
通讯作者：
Itoh, Tomoo
影响因子：
3.4
作者：
Knights, Kathleen M.;Rowland, Andrew;Miners, John O.
通讯作者：
Miners, John O.
影响因子：
3
作者：
DOSREMEDIOS, CG;MOENS, PDJ
通讯作者：
MOENS, PDJ
DOI：
10.1016/j.bbagen.2016.04.011
发表时间：
2016-07-01
影响因子：
3
作者：
Agrawal, Ruchi;Kumar, Prem, V;Saini, Deepak Kumar
通讯作者：
Saini, Deepak Kumar
影响因子：
2.1
作者：
Fujiwara, Ryoichi;Nakajima, Miki;Yokoi, Tsuyoshi
通讯作者：
Yokoi, Tsuyoshi