Evidence map›Paper›PMID 40344218›Full record

ArticleFEBS letters2025

Modifications in FLAP's second cytosolic loop influence 5-LOX interaction, inhibitor binding, and leukotriene formation.

Erik Romp, Katharina Rataj, Stefanie König, Marcia E Newcomer, Oliver Werz, Ulrike Garscha

Abstract read
In one paragraph

Article in FEBS letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

6 authors.

Erik RompDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Germany.
Katharina RatajDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Greifswald University, Germany.
Stefanie KönigDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Greifswald University, Germany.
Marcia E NewcomerDepartment of Biological Sciences, Louisiana State University, Baton Rouge, LA, USA.
Oliver WerzDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Germany.ORCID https://orcid.org/0000-0002-5064-4379
Ulrike GarschaDepartment of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Greifswald University, Germany.ORCID https://orcid.org/0000-0002-3645-7833

Funding

Deutsche Forschungsgemeinschaft GA-2101/2-1
6 · The paper itself

Abstract

Leukotrienes, synthesized via the 5-lipoxygenase (5-LOX) pathway in the arachidonic acid cascade, are critical in inflammation. Effective leukotriene production requires interaction between 5-LOX and 5-LOX-activating protein (FLAP) at the nuclear membrane. This study used site-directed mutagenesis to explore amino acid residues in FLAP's inhibitor binding pocket and cytosolic loops, assessing their impact on 5-LOX product formation, the FLAP inhibitor MK886's efficacy, 5-LOX translocation, and 5-LOX/FLAP complex formation. Mutations in the second cytosolic loop, especially at residue S108, reduced MK886 potency and disrupted 5-LOX/FLAP complex formation. These results highlight the second cytosolic loop of FLAP in the 5-LOX/FLAP interaction and proper leukotriene formation and suggest that targeting this region could aid in the development of new FLAP inhibitors with improved pharmacokinetics.

Indexed as

complex formationinflammationleukotrienelipid mediatorlipoxygenasemutagenesis

Identifiers

PMID40344218
PMCPMC12338864

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Registered trials

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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.