Crystal structures of Lymphocytic choriomeningitis virus endonuclease domain complexed with diketo-acid ligands

IUCrJ
Magali Saez-AyalaFrançois Ferron

Abstract

The Arenaviridae family, together with the Bunyaviridae and Orthomyxoviridae families, is one of the three negative-stranded RNA viral families that encode an endonuclease in their genome. The endonuclease domain is at the N-terminus of the L protein, a multifunctional protein that includes the RNA-dependent RNA polymerase. The synthesis of mRNA in arenaviruses is a process that is primed by capped nucleotides that are 'stolen' from the cellular mRNA by the endonuclease domain in cooperation with other domains of the L protein. This molecular mechanism has been demonstrated previously for the endonuclease of the prototype Lymphocytic choriomeningitis virus (LCMV). However, the mode of action of this enzyme is not fully understood as the original structure did not contain catalytic metal ions. The pivotal role played by the cap-snatching process in the life cycle of the virus and the highly conserved nature of the endonuclease domain make it a target of choice for the development of novel antiviral therapies. Here, the binding affinities of two diketo-acid (DKA) compounds (DPBA and L-742,001) for the endonuclease domain of LCMV were evaluated using biophysical methods. X-ray structures of the LCMV endonuclease domain with cataly...Continue Reading

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Citations

Oct 5, 2019·Nucleic Acids Research·Rhian JonesJuan Reguera
Sep 28, 2020·Antiviral Research·Yaiza Fernández-GarcíaJoana Rocha-Pereira

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Methods Mentioned

BETA
PCR
microscale thermophoresis
isothermal titration calorimetry

Software Mentioned

MMTK
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BKChem

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