ArticleBiochemistry2009
Structural and kinetic analyses of macrophage migration inhibitory factor active site interactions.
Article in Biochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
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.
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Who cites it
23 citing papers in PubMed, 53 citations in OpenAlex.
- Identification of a key water molecule involved in the macrophage migration inhibitory factor-catalyzed tautomerization of para-hydroxyphenylpyruvate using neutron crystallography.Protein science : a publication of the Protein Society · 2026Article
- Attempts to Achieve Targeted Covalent Inhibition of Hsp90β.Chemical biology & drug design · 2026Article
- Identification of a novel and high affinity MIF inhibitorJournal of enzyme inhibition and medicinal chemistry · 2025Article
- Synthesis of Epoxyoxirenes: Phytotoxic Activity and Enzymatic Target Identification.Plants (Basel, Switzerland) · 2025Article
- Iguratimod, an allosteric inhibitor of macrophage migration inhibitory factor (MIF), prevents mortality and oxidative stress in a murine model of acetaminophen overdose.Molecular medicine (Cambridge, Mass.) · 2024Article
- Allosteric Inhibitors of Macrophage Migration Inhibitory Factor (MIF) Interfere with Apoptosis-Inducing Factor (AIF) Co-Localization to Prevent Parthanatos.Journal of medicinal chemistry · 2023Article
- Discovery of novel MIF inhibitors that attenuate microglial inflammatory activation by structures-based virtual screening and in vitro bioassays.Acta pharmacologica Sinica · 2022Article
- Tetralone derivatives are MIF tautomerase inhibitors and attenuate macrophage activation and amplify the hypothermic response in endotoxemic mice.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Regulation of MIF Enzymatic Activity by an Allosteric Site at the Central Solvent Channel.Cell chemical biology · 2020Article
- Post-translational regulation of macrophage migration inhibitory factor: Basis for functional fine-tuning.Redox biology · 2018Review
- Structural basis for decreased induction of class IB PI3-kinases expression by MIF inhibitors.Journal of cellular and molecular medicine · 2017Article
- Role of macrophage migration inhibitory factor in age-related lung disease.American journal of physiology. Lung cellular and molecular physiology · 2015Review
- Sulfonyl fluorides as privileged warheads in chemical biology.Chemical science · 2015Article
- Diversity and Inter-Connections in the CXCR4 Chemokine Receptor/Ligand Family: Molecular Perspectives.Frontiers in immunology · 2015Review
- The modern pharmacology of paracetamol: therapeutic actions, mechanism of action, metabolism, toxicity and recent pharmacological findings.Inflammopharmacology · 2013Review
- Structural interactions dictate the kinetics of macrophage migration inhibitory factor inhibition by different cancer-preventive isothiocyanates.Biochemistry · 2012Article
- A novel allosteric inhibitor of macrophage migration inhibitory factor (MIF).The Journal of biological chemistry · 2012Article
- Thiadiazolidinones: a new class of alanine racemase inhibitors with antimicrobial activity against methicillin-resistant Staphylococcus aureus.Biochemical pharmacology · 2012Article
- Discovery of potent and selective inhibitors of human platelet-type 12- lipoxygenase.Journal of medicinal chemistry · 2011Article
- Optimization of N-benzyl-benzoxazol-2-ones as receptor antagonists of macrophage migration inhibitory factor (MIF).Bioorganic & medicinal chemistry letters · 2010Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Macrophage migration inhibitory factor (MIF) is a secreted protein expressed in numerous cell types that counters the antiinflammatory effects of glucocorticoids and has been implicated in sepsis, cancer, and certain autoimmune diseases. Interestingly, the structure of MIF contains a catalytic site resembling the tautomerase/isomerase sites of microbial enzymes. While bona fide physiological substrates remain unknown, model substrates have been identified. Selected compounds that bind in the tautomerase active site also inhibit biological functions of MIF. It had previously been shown that the acetaminophen metabolite, N-acetyl-p-benzoquinone imine (NAPQI), covalently binds to the active site of MIF. In this study, kinetic data indicate that NAPQI inhibits MIF both covalently and noncovalently. The structure of MIF cocrystallized with NAPQI reveals that the NAPQI has undergone a chemical alteration forming an acetaminophen dimer (bi-APAP) and binds noncovalently to MIF at the mouth of the active site. We also find that the commonly used protease inhibitor, phenylmethylsulfonyl fluoride (PMSF), forms a covalent complex with MIF and inhibits the tautomerase activity. Crystallographic analysis reveals the formation of a stable, novel covalent bond for PMSF between the catalytic nitrogen of the N-terminal proline and the sulfur of PMSF with complete, well-defined electron density in all three active sites of the MIF homotrimer. Conclusions are drawn from the structures of these two MIF-inhibitor complexes regarding the design of novel compounds that may provide more potent reversible and irreversible inhibition of MIF.
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Registered trials
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.