| Title |
Inter-isoform Hetero-dimerization of Human UDP-Glucuronosyltransferases (UGTs) 1A1, 1A9 and 2B7 and Impacts on Glucuronidation Activity
|
|---|---|
| Published in |
Scientific Reports, November 2016
|
| DOI | 10.1038/srep34450 |
| Pubmed ID | |
| Authors |
Ling-Min Yuan, Zhang-Zhao Gao, Hong-Ying Sun, Sai-Nan Qian, Yong-Sheng Xiao, Lian-Li Sun, Su Zeng |
| Abstract |
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. |
Mendeley readers
The data shown below were compiled from readership statistics for 12 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 12 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Bachelor | 2 | 17% |
| Researcher | 2 | 17% |
| Professor | 2 | 17% |
| Lecturer > Senior Lecturer | 1 | 8% |
| Other | 1 | 8% |
| Other | 2 | 17% |
| Unknown | 2 | 17% |
| Readers by discipline | Count | As % |
|---|---|---|
| Chemistry | 5 | 42% |
| Agricultural and Biological Sciences | 2 | 17% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 17% |
| Unknown | 3 | 25% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 08 March 2018.
All research outputs
#7,547,578
of 23,026,672 outputs
Outputs from Scientific Reports
#51,440
of 124,372 outputs
Outputs of similar age
#138,015
of 416,702 outputs
Outputs of similar age from Scientific Reports
#1,446
of 3,285 outputs
Altmetric has tracked 23,026,672 research outputs across all sources so far. This one is in the 44th percentile – i.e., 44% of other outputs scored the same or lower than it.
So far Altmetric has tracked 124,372 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 18.2. This one has gotten more attention than average, scoring higher than 56% of its peers.
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We're also able to compare this research output to 3,285 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 51% of its contemporaries.