Kimble Amber D, Dawson Omolara C O, Liu Lijun, Subramanian Sandhya, Cooper Anne, Battaile Kevin, Craig Justin, Harmon Elizabeth, Myler Peter, Lovell Scott, Asojo Oluwatoyin A
Department of Clinical Laboratory Science, College of Nursing and Allied Health Sciences, Howard University, 801 North Capitol Street, 4th Floor, Washington, DC 20002, USA.
Grafton High School USA, 403 Grafton Drive, Yorktown, VA 23692, USA.
Acta Crystallogr F Struct Biol Commun. 2024 Dec 1;80(Pt 12):328-34. doi: 10.1107/S2053230X24010550.
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-OvMIF-1). OvMIF-1 is a possible drug target. His-OvMIF-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 OvMIF-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 OvMIF-1 because size-exclusion chomatographic analysis of His-OvMIF-1 suggests a monomer, while PISA analysis suggests a hexamer stabilized by the unique C-terminal tails.
盘尾丝虫可导致失明、盘尾丝虫病、皮肤感染以及诸如点头综合征等严重的神经系统疾病。由于目前使用的药物伊维菌素对孕妇和同时感染罗阿丝虫的患者禁用，因此需要新的治疗方法。西雅图传染病结构基因组学中心（SSGCID）制备、结晶并确定了N端带有六组氨酸标签的盘尾丝虫巨噬细胞迁移抑制因子-1（His-OvMIF-1）的无配体结构。OvMIF-1是一个潜在的药物靶点。His-OvMIF-1具有独特的水母样结构，以典型的巨噬细胞迁移抑制因子（MIF）三聚体作为“头部”，并具有独特的C端“尾部”。去除N端标签后得到的OvMIF-1结构具有比人MIF中观察到的更大的腔，可用于药物再利用和发现的靶向。由于对His-OvMIF-1的尺寸排阻色谱分析表明其为单体，而PISA分析表明其为通过独特的C端尾部稳定的六聚体，因此有必要去除标签以确定OvMIF-1的实际生物学寡聚体。
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