Crystal structure of N-terminally hexahistidine-tagged Onchocerca volvulus macrophage migration inhibitory factor-1
Onchocerca volvulus causes blindness, onchocerciasis, skin infections and devastating neurological diseases such as nodding syndrome. New treatments are needed because the currently used drug, ivermectin, is contraindicated in pregnant women and those co-infected with Loa loa . The Seattle Structural Genomics Center for Infectious Disease (SSGCID) produced, crystallized and determined the apo structure of N-terminally hexahistidine-tagged O. volvulus macrophage migration inhibitory factor-1 (His- Ov MIF-1). Ov MIF-1 is a possible drug target. His- Ov MIF-1 has a unique jellyfish-like structure with a prototypical macrophage migration inhibitory factor (MIF) trimer as the `head' and a unique C-terminal `tail'. Deleting the N-terminal tag reveals an Ov MIF-1 structure with a larger cavity than that observed in human MIF that can be targeted for drug repurposing and discovery. Removal of the tag will be necessary to determine the actual biological oligomer of Ov MIF-1 because size-exclusion chomatographic analysis of His- Ov MIF-1 suggests a monomer, while PISA analysis suggests a hexamer stabilized by the unique C-terminal tails.
- Sponsoring Organization:
- USDOE
- Grant/Contract Number:
- SC0012704
- OSTI ID:
- 2476419
- Journal Information:
- Acta Crystallographica. Section F, Structural Biology Communications, Journal Name: Acta Crystallographica. Section F, Structural Biology Communications Journal Issue: 12 Vol. 80; ISSN ACSFEN; ISSN 2053-230X
- Publisher:
- International Union of Crystallography (IUCr)Copyright Statement
- Country of Publication:
- United Kingdom
- Language:
- English
Similar Records
Influence of cadmium, lead, and zinc on the ability of guinea pig macrophages to interact with macrophage migration inhibitory factor
Structural and Functional Characterization of a Secreted Hookworm Macrophage Migration Inhibitory Factor (MIF) that Interacts with the Human MIF Receptor CD74