FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2012759923> ?p ?o ?g. }

• W2012759923 endingPage "102" @default.
• W2012759923 startingPage "85" @default.
• W2012759923 abstract "The molecular mechanism of action of macrophage migration inhibitory factor (MIF), a cytokine with a critical role in the immune and inflammatory response, has not yet been identified. Here we report that MIF can function as an enzyme exhibiting thiol-protein oxidoreductase activity. Using a decapeptide fragment of MIF (MF1) spanning the conserved cysteine sequence motif Cys57-Ala-Leu-Cys60 (CALC), Cys → Ser mutants (C57S MIF, C60S MIF, and C57S/C60S MIF) of human MIF (wtMIF), and alkylated wtMIF, we show that this activity is mediated by the CALC region and is important for the macrophage-activating properties of MIF. Both wtMIF and MF1 were demonstrated to form an intramolecular disulfide bridge. Using two common oxidoreductase assays, MIF was shown to enzymatically catalyze the reduction of insulin and 2-hydroxyethyldisulfide (HED). Examination of wtMIF and the mutants by far-UV circular dichroism spectroscopy (CD) together with denaturation studies showed that substituting or reducing the cysteine residues of CALC led to a reduced conformational stability of MIF but did not significantly change its overall conformation. A functional role for the CALC region was revealed by subjecting the mutants and alkylated wtMIF to the enzymatic assays. Mutant C60S did not have any enzymatic activity while mutant C57S had a reduced activity. Thiol-modified wtMIF that was alkylated under oxidizing conditions was found to have full enzymatic activity, whereas alkylation of wtMIF under reducing conditions completely eliminated MIF-mediated redox activity. Importantly, further physiological relevance of the disulfide motif was obtained by examining the mutants and alkylated MIF in an immunological assay that involved the macrophage-activating properties of MIF. In this test, mutant C60S was essentially inactive and mutant C57S was partly active, indicating together that at least some of the cytokine-like biological activities of MIF are dependent on the presence of cysteine 57 and 60. Again, use of the alkylated MIF species confirmed the role of the cysteine motif for this MIF activity. In conclusion, our results argue (a) that MIF exhibits enzymatic oxidoreductase activity, (b) that this activity is dependent on the presence of the catalytic center that is formed by cysteine residues 57 and 60, and (c) that certain MIF-mediated immune processes are due to the cysteine-mediated redox mechanism." @default.
• W2012759923 created "2016-06-24" @default.
• W2012759923 creator A5001664185 @default.
• W2012759923 creator A5002958420 @default.
• W2012759923 creator A5015723785 @default.
• W2012759923 creator A5017854650 @default.
• W2012759923 creator A5032494718 @default.
• W2012759923 creator A5033269665 @default.
• W2012759923 creator A5054344760 @default.
• W2012759923 creator A5055917278 @default.
• W2012759923 creator A5063674598 @default.
• W2012759923 date "1998-07-01" @default.
• W2012759923 modified "2023-10-03" @default.
• W2012759923 title "Disulfide analysis reveals a role for macrophage migration inhibitory factor (MIF) as thiol-protein oxidoreductase" @default.
• W2012759923 cites W109149868 @default.
• W2012759923 cites W1487001072 @default.
• W2012759923 cites W1497815806 @default.
• W2012759923 cites W1501442799 @default.
• W2012759923 cites W1510912973 @default.
• W2012759923 cites W1512686244 @default.
• W2012759923 cites W1526318640 @default.
• W2012759923 cites W1547929361 @default.
• W2012759923 cites W1548745574 @default.
• W2012759923 cites W1551340508 @default.
• W2012759923 cites W1554148351 @default.
• W2012759923 cites W1564327094 @default.
• W2012759923 cites W1584729364 @default.
• W2012759923 cites W1593567129 @default.
• W2012759923 cites W1593932996 @default.
• W2012759923 cites W1788190869 @default.
• W2012759923 cites W1842535138 @default.
• W2012759923 cites W1979244891 @default.
• W2012759923 cites W1982800604 @default.
• W2012759923 cites W1995855154 @default.
• W2012759923 cites W1997838054 @default.
• W2012759923 cites W1997870466 @default.
• W2012759923 cites W2006370393 @default.
• W2012759923 cites W2009947721 @default.
• W2012759923 cites W2012716149 @default.
• W2012759923 cites W2019535641 @default.
• W2012759923 cites W2023939320 @default.
• W2012759923 cites W2026192283 @default.
• W2012759923 cites W2026274889 @default.
• W2012759923 cites W2026676900 @default.
• W2012759923 cites W2032439102 @default.
• W2012759923 cites W2036357948 @default.
• W2012759923 cites W2036503551 @default.
• W2012759923 cites W2039111250 @default.
• W2012759923 cites W2039984088 @default.
• W2012759923 cites W2043025348 @default.
• W2012759923 cites W2048585596 @default.
• W2012759923 cites W2052614246 @default.
• W2012759923 cites W2055307767 @default.
• W2012759923 cites W2059448081 @default.
• W2012759923 cites W2062824264 @default.
• W2012759923 cites W2066372869 @default.
• W2012759923 cites W2072898315 @default.
• W2012759923 cites W2075954862 @default.
• W2012759923 cites W2081710997 @default.
• W2012759923 cites W2082017122 @default.
• W2012759923 cites W2087795097 @default.
• W2012759923 cites W2090056328 @default.
• W2012759923 cites W2090338919 @default.
• W2012759923 cites W2101019091 @default.
• W2012759923 cites W2116076986 @default.
• W2012759923 cites W2122151701 @default.
• W2012759923 cites W2126600660 @default.
• W2012759923 cites W2133067061 @default.
• W2012759923 cites W2146058212 @default.
• W2012759923 cites W2149653798 @default.
• W2012759923 cites W2203044109 @default.
• W2012759923 cites W2230507390 @default.
• W2012759923 cites W337892304 @default.
• W2012759923 cites W4247896860 @default.
• W2012759923 cites W4322387796 @default.
• W2012759923 doi "https://doi.org/10.1006/jmbi.1998.1864" @default.
• W2012759923 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/9653033" @default.
• W2012759923 hasPublicationYear "1998" @default.
• W2012759923 type Work @default.
• W2012759923 sameAs 2012759923 @default.
• W2012759923 citedByCount "284" @default.
• W2012759923 countsByYear W20127599232012 @default.
• W2012759923 countsByYear W20127599232013 @default.
• W2012759923 countsByYear W20127599232014 @default.
• W2012759923 countsByYear W20127599232015 @default.
• W2012759923 countsByYear W20127599232016 @default.
• W2012759923 countsByYear W20127599232017 @default.
• W2012759923 countsByYear W20127599232018 @default.
• W2012759923 countsByYear W20127599232019 @default.
• W2012759923 countsByYear W20127599232020 @default.
• W2012759923 countsByYear W20127599232021 @default.
• W2012759923 countsByYear W20127599232022 @default.
• W2012759923 countsByYear W20127599232023 @default.
• W2012759923 crossrefType "journal-article" @default.
• W2012759923 hasAuthorship W2012759923A5001664185 @default.
• W2012759923 hasAuthorship W2012759923A5002958420 @default.
• W2012759923 hasAuthorship W2012759923A5015723785 @default.
• W2012759923 hasAuthorship W2012759923A5017854650 @default.

• next