Structure of the Murray Valley encephalitis virus RNA helicase at 1.9 Å resolution

Abstract

Murray Valley encephalitis virus (MVEV), a mosquito‐borne flavivirus endemic to Australia, is closely related to Japanese encephalitis virus and West Nile virus. Nonstructural protein 3 (NS3) is a multifunctional enzyme with serine protease and DEXH/D‐box helicase domains, whose activity is central to flavivirus replication and is therefore a possible target for anti‐flaviviral compounds. Cloning, purification, and crystal structure determination to 1.9 Å resolution of the NS3 helicase of MVEV and characterization of its enzymatic activity is reported. Comparison with the structures of helicases from related viruses supports a possible mechanism of ATP hydrolysis‐driven strand separation.