Dimerization-Induced Allosteric Changes of the Oxyanion-Hole Loop Activate the Pseudorabies Virus Assemblin pUL26N, a Herpesvirus Serine Protease

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Herpesviruses encode a unique serine protease, which is essential for herpesvirus capsid maturation and is therefore an interesting target for drug development. In solution, this protease exists in an equilibrium of an inactive monomeric and an active dimeric form. All currently available crystal structures of herpesvirus proteases represent complexes, particularly dimers. Here we show the first three-dimensional structure of the native monomeric form in addition to the native and the chemically inactivated dimeric form of the protease derived from the porcine herpesvirus pseudorabies virus. Comparison of the monomeric and dimeric form allows predictions on the structural changes that occur during dimerization and shed light onto the process of protease activation. These new crystal structures provide a rational base to develop drugs preventing dimerization and therefore impeding herpesvirus capsid maturation. Furthermore, it is likely that this mechanism is conserved throughout the herpesviruses.

Vyšlo v časopise: Dimerization-Induced Allosteric Changes of the Oxyanion-Hole Loop Activate the Pseudorabies Virus Assemblin pUL26N, a Herpesvirus Serine Protease. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005045
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005045

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