Role of cysteine-58 and cysteine-95 residues in the thiol di-sulfide oxidoreductase activity of Macrophage Migration Inhibitory Factor-2 of Wuchereria bancrofti

Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (DDT): Pathways to Tumorigenesis and Therapeutic Opportunities

“…Modeling of MIF and DDT structures is depicted in Figure 1a. Unlike MIF, DDT lacks the pseudo-ELR domain required for CXCR2 binding and is therefore unable to signal through this receptor [12,13]. An overview of MIF and DDT chemokine interactions with its cognate (CD74) and non-cognate (CXCR2, 4, 7) receptors is outlined in Figure 1c.…”

“…Imalumab is a human recombinant antibody targeted against a MIF epitope associated with its oxidation (oxMIF), which may arise in oxidative inflammatory environments, offering a more selective target that spares MIF functions in normal physiology [221,222]. Of note, DDT lacks the CXXC motif crucial for MIF's redox sensing and may not be targeted by Imalumab [12,13]. In the Phase I trial NCT01765790, the safety of Imalumab was tested in patients with advanced solid tumors and exhibited successful tumor penetration and activation of apoptotic pathways.…”

Nematode Orthologs of Macrophage Migration Inhibitory Factor (MIF) as Modulators of the Host Immune Response and Potential Therapeutic Targets

“…Homology modeling showed that of two of three cysteine residues (Cys58 and Cys95) are nearby (3.23 Å) in the tertiary structure with a pKa value of 9, indicating that they may play a role in the catalytic activity of disulfide oxidoreductase. Mutagenesis of these residues resulted in the lack of oxidoreductase activity in the insulin reduction assay, indicating that these two cysteines are crucial for the catalytic activity of Wba-MIF-2 [66,78]. 1; hMIF accession number: CAG30406.1.…”

Filarial Parasite-Derived New Potential Bio-Therapeutic Agents For Inflammatory Bowel Diseases

“…Therefore, there has been significant interest among researchers to identify the immunomodulatory molecules of lymphatic filarial parasites that have significant immunosuppressive effect in experimental autoimmune diseases [27,[30][31][32][33][34]. Several filarial derived molecules have been identified as immunomodulatory agents, such as mammalian cytokine homologs, Abundant Larval Transcript (ALT) antigens, macrophage migration inhibitory factor (MIF), cysteine proteases and venom allergen-like proteins [35][36][37][38]. This commentary will focus mainly on the biotherapeutic properties of cysteine proteases and MIF.…”