Evidence map›Paper›PMID 39448635›Full record

ArticleNature communications2024

Structural insights into the inhibition mechanism of fungal GWT1 by manogepix.

Xinli Dai, Xuanzhong Liu, Jialu Li, Hui Chen, Chuangye Yan, Yaozong Li, Hanmin Liu, Dong Deng, Xiang Wang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
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

14 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. New Perspectives on Antimicrobial Agents: Fosmanogepix.Antimicrobial agents and chemotherapy · 2026
    Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. 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

9 authors.

Xinli Dai *Department of Obstetrics, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, China.
Xuanzhong Liu *Department of Obstetrics, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, China.
Jialu Li *Department of Obstetrics, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, China.ORCID 0000-0002-0513-7597
Hui Chen *Department of Obstetrics, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, China.
Chuangye YanState Key Laboratory of Membrane Biology, Beijing Frontier Research Center for Biological Structure, Tsinghua-Peking Joint Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China.
Yaozong LiDepartment of Chemistry, Umeå University, SE-901 87, Umeå, Sweden.ORCID 0000-0002-5796-2644
Hanmin LiuDepartment of Obstetrics, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, China. liuhm@scu.edu.cn.
Dong DengDepartment of Obstetrics, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, China. dengd@scu.edu.cn.ORCID 0000-0002-8590-9525
Xiang WangDepartment of Obstetrics, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, Chengdu, China. xiangwang@scu.edu.cn.ORCID 0000-0001-9348-7441

Funding

National Natural Science Foundation of China (National Science Foundation of China) 31971132National Natural Science Foundation of China (National Science Foundation of China) 32100979National Natural Science Foundation of China (National Science Foundation of China) 32171211National Natural Science Foundation of China (National Science Foundation of China) 32471264
6 · The paper itself

Abstract

Glycosylphosphatidylinositol (GPI) acyltransferase is crucial for the synthesis of GPI-anchored proteins. Targeting the fungal glycosylphosphatidylinositol acyltransferase GWT1 by manogepix is a promising antifungal strategy. However, the inhibitory mechanism of manogepix remains unclear. Here, we present cryo-EM structures of yeast GWT1 bound to the substrate (palmitoyl-CoA) and inhibitor (manogepix) at 3.3 Å and 3.5 Å, respectively. GWT1 adopts a unique fold with 13 transmembrane (TM) helixes. The palmitoyl-CoA inserts into the chamber among TM4, 5, 6, 7, and 12. The crucial residues (D145 and K155) located on the loop between TM4 and TM5 potentially bind to the GPI precursor, contributing to substrate recognition and catalysis, respectively. The antifungal drug, manogepix, occupies the hydrophobic cavity of the palmitoyl-CoA binding site, suggesting a competitive inhibitory mechanism. Structural analysis of resistance mutations elucidates the drug specificity and selectivity. These findings pave the way for the development of potent and selective antifungal drugs targeting GWT1.

Indexed as

AcyltransferasesAntifungal AgentsCryoelectron MicroscopyBinding SitesFungal ProteinsModels, MolecularSaccharomyces cerevisiaeAcyltransferasesAntifungal AgentsFungal Proteinsglycylpeptide N-tetradecanoyltransferase

Identifiers

PMID39448635
PMCPMC11502805

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.