Evidence map›Paper›PMID 31655060›Full record

ArticleiScience2019

Revealing a Mutant-Induced Receptor Allosteric Mechanism for the Thyroid Hormone Resistance.

Benqiang Yao, Yijuan Wei, Shuchi Zhang, Siyu Tian, Shuangshuang Xu, Rui Wang, Weili Zheng, Yong Li

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. KDIGO 2026 Clinical Practice Guideline for Anemia in Chronic Kidney Disease (CKD): a commentary from the European Renal Best Practice (ERBP).Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026
    Article
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  7. Review
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  17. Article
  18. Review
  19. Roxadustat: Do we know all the answers?Biomolecules & biomedicine · 2023
    Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Benqiang YaoState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Fujian 361005, China.
Yijuan WeiState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Fujian 361005, China.
Shuchi ZhangState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Fujian 361005, China.
Siyu TianState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Fujian 361005, China.
Shuangshuang XuState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Fujian 361005, China.
Rui WangState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Fujian 361005, China.
Weili ZhengState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Fujian 361005, China.
Yong LiState Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Fujian 361005, China. Electronic address: yongli@xmu.edu.cn.
Xiamen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Resistance to thyroid hormone (RTH) is a clinical disorder without specific and effective therapeutic strategy, partly due to the lack of structural mechanisms for the defective ligand binding by mutated thyroid hormone receptors (THRs). We herein uncovered the prescription drug roxadustat as a novel THRβ-selective ligand with therapeutic potentials in treating RTH, thereby providing a small molecule tool enabling the first probe into the structural mechanisms of RTH. Despite a wide distribution of the receptor mutation sites, different THRβ mutants induce allosteric conformational modulation on the same His435 residue, which disrupts a critical hydrogen bond required for the binding of thyroid hormones. Interestingly, roxadustat retains hydrophobic interactions with THRβ via its unique phenyl extension, enabling the rescue of the activity of the THRβ mutants. Our study thus reveals a critical receptor allosterism mechanism for RTH by mutant THRβ, providing a new and viable therapeutic strategy for the treatment of RTH.

Indexed as

Biological SciencesMolecular BiologyStructural Biology

Identifiers

PMID31655060
PMCPMC6806671
OpenAlexW2978490545

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.