Get “Hooked” On Brugia malayi Asparaginyl tRNA Synthetase

Abstract

A partnership between the Brown Deer High School students participating in the MSOE SMART Team (Students Modeling A Research Topic) program and a scientist enabled the team to explore asparaginyl‐tRNA synthetase (AsnRS), a potential drug target to treat lymphatic filariasis, and to build a 3D physical model of the protein. Lymphatic filariasis results from mosquitoes transferring the nematode, Brugia malayi, to host lymph nodes, leading to swelling of affected limbs. AsnRS hooks asparagine to tRNA, used during protein synthesis. AsnRS is a member of the aminoacyl tRNA synthetase (AARS) family, a set of structurally heterogenous enzymes, specific for each amino acid. AARS are potential drug targets as they are essential for survival and are structurally different between species. AARS also functions as an immunosuppressant, blocking interleukin 8 receptors in humans. Current research for treatment targets parasitic AARS. If multiple functions could be mapped to the same region of the protein, a single drug could target these functions. Inhibition of the tRNA‐aminocylation function of AsnRS would prevent protein synthesis, thus causing death of the parasite. Preventing AsnRS from blocking interleukin 8 receptors, would act as an immunostimulant in humans. Further research on this family of enzymes could provide alternative therapies to treating parasitic diseases. Supported by a grant from NIH‐NCRR‐SEPA.