Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor

• Autores: Ke-Jian Lei, Guido Hansen, Christoph Nitsche
• Localización: Science, ISSN 0036-8075, Vol. 353, Nº 6298, 2016, págs. 504-505
• Idioma: inglés
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• Resumen

  • The ongoing Zika virus (ZIKV) outbreak is linked to severe neurological disorders. ZIKV relies on its NS2B/NS3 protease for polyprotein processing; hence, this enzyme is an attractive drug target. The 2.7 angstrom; crystal structure of ZIKV protease in complex with a peptidomimetic boronic acid inhibitor reveals a cyclic diester between the boronic acid and glycerol. The P2 4-aminomethylphenylalanine moiety of the inhibitor forms a salt-bridge with the nonconserved Asp83 of NS2B; ion-pairing between Asp83 and the P2 residue of the substrate likely accounts for the enzyme’s high catalytic efficiency. The unusual dimer of the ZIKV protease:inhibitor complex seen in the crystal may provide a model for assemblies formed at high local concentrations of protease at the endoplasmatic reticulum membrane, the site of polyprotein processing.