Evidence map›Paper›PMID 25016026›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014

Targeting distinct tautomerase sites of D-DT and MIF with a single molecule for inhibition of neutrophil lung recruitment.

Deepa Rajasekaran, Swen Zierow, Mansoor Syed, Richard Bucala, Vineet Bhandari, Elias J Lolis

Abstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
2.0field-weighted citation impact, top 14% 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

46 citing papers in PubMed, 86 citations in OpenAlex.

  1. Crystal structure of Plasmodium vivax macrophage migration inhibitory factor.Acta crystallographica. Section F, Structural biology communications · 2026
    Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. In vivo synergistic enhancement of MIF-mediated inflammation in acute lung injury by the plant ortholog Arabidopsis MDL1.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  7. Article
  8. Article
  9. Structures of Trichomonas vaginalis macrophage migratory inhibitory factor.Acta crystallographica. Section F, Structural biology communications · 2024
    Article
  10. Review
  11. MIF contribution to progressive brain diseases.Journal of neuroinflammation · 2024
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. 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

6 authors at 1 institution in 1 country.

Deepa RajasekaranDepartment of Pharmacology.
Swen ZierowDepartment of Pharmacology.
Mansoor SyedDepartment of Pediatrics.
Richard BucalaDepartment of Internal Medicine, and Yale Cancer Center, Yale University, New Haven, Connecticut, USA.
Vineet BhandariDepartment of Pediatrics.
Elias J LolisDepartment of Pharmacology, Yale Cancer Center, Yale University, New Haven, Connecticut, USA elias.lolis@yale.edu.
Yale University · US

Funding

Mechanisms of Rheumatoid Synovial Fibroblast ActivationR01AR049610 · NIAMS · YALE UNIVERSITY · PI BUCALA, RICHARD J · 2002 to 2018
$5.0M
Regulation of CXCR4 by cognate and non-cognate ligandsR01AI082295 · NIAID · YALE UNIVERSITY · PI LOLIS, ELIAS · 2009 to 2013
$2.0M
Functional and Structural Studies of CD74 ActivationR01AI065029 · NIAID · YALE UNIVERSITY · PI LOLIS, ELIAS · 2006 to 2010
$2.0M
NIAID NIH HHS R01 AI065029NIAID NIH HHS R01 AI082295NIAMS NIH HHS R01 AR049610
6 · The paper itself

Abstract

We report a new inflammatory activity for extracellular d-dopachrome tautomerase (D-DT), the recruitment of neutrophils to the lung on D-DT intratracheal installation of C57BL/6J mice with an EC50 of 5.6 μg. We also find that D-DT and macrophage migration inhibitory factor (MIF) have additive effects in neutrophil recruitment. Although the tautomerase site of D-DT and its homologue MIF are biophysically very different, 4-iodo-6-phenylpyrimidine (4-IPP) forms a covalent bond with Pro-1 of both proteins, resulting in a 6-phenylpyrimidine (6-PP) adduct. Recruitment of neutrophils to the lung for the 6-PP adducts of D-DT and MIF are reduced by ∼ 50% relative to the apo proteins, demonstrating that an unmodified Pro-1 is important for this activity, but there is no cooperativity in inhibition of the proteins together. The differences in the binding mode of the 6-PP adduct for D-DT was determined by crystallographic studies at 1.13 Å resolution and compared to the structure of the MIF-6-PP complex. There are major differences in the location of the 6-PP adduct to the D-DT and MIF active sites that provide insight into the lack of cooperativity by 4-IPP and into tuning the properties of the covalent inhibitors of D-DT and MIF that are necessary for the development of therapeutic small molecules against neutrophil damage from lung infections such as Pseudomonas aeruginosa in cystic fibrosis and immunocompromised patients.

Indexed as

AnimalsCatalytic DomainCell MovementIntramolecular OxidoreductasesLungMacrophage Migration-Inhibitory FactorsMice, Inbred C57BLModels, MolecularNeutrophil InfiltrationNeutrophilsPyrimidines4-iodo-6-phenylpyrimidinedopachrome isomeraseIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsMif protein, mousePyrimidines4-IPPcovalent inhibitor

Identifiers

PMID25016026
PMCPMC4200328
OpenAlexW2083244808

What OpenQuestion holds

Textmetadata
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.