6bg6
From Proteopedia
Crystal structure of S111A mutant of human macrophage migration inhibitory factor
Structural highlights
Disease[MIF_HUMAN] Genetic variations in MIF are associated with susceptibility to rheumatoid arthritis systemic juvenile (RASJ) [MIM:604302]. An inflammatory articular disorder with systemic-onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. Function[MIF_HUMAN] Pro-inflammatory cytokine. Involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity.[1] [2] Publication Abstract from PubMedMacrophage migration inhibitory factor (MIF) activates CD74, which leads to severe disorders including inflammation, autoimmune diseases and cancer under pathological conditions. Molecular dynamics (MD) simulations up to one microsecond revealed dynamical correlation between a residue located at the opening of one end of the MIF solvent channel, previously thought to be a consequence of homotrimerization, and residues in a distal region responsible for CD74 activation. Experiments verified the allosteric regulatory site and identified a pathway to this site via the MIF beta-strands. The reported findings provide fundamental insights on a dynamic mechanism that controls the MIF-induced activation of CD74. Nanosecond Dynamics Regulate the MIF-Induced Activity of CD74.,Pantouris G, Ho J, Shah D, Syed MA, Leng L, Bhandari V, Bucala R, Batista VS, Loria JP, Lolis EJ Angew Chem Int Ed Engl. 2018 Apr 18. doi: 10.1002/anie.201803191. PMID:29669180[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Lolis, E | Pantouris, G | Isomerase | Mutation | Surface
