5LC0

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

Summary for 5LC0

• Entry DOI: 10.2210/pdb5lc0/pdb
• Descriptor: NS2B-NS3 protease,NS2B-NS3 protease, N-((S)-3-(4-(aminomethyl)phenyl)-1-(((R)-4-guanidino-1-(5-hydroxy-1,3,2-dioxaborinan-2-yl)butyl)amino)-1-oxopropan-2-yl)benzamide (3 entities in total)
• Functional Keywords: zika virus ns2b-ns3 protease, antiviral agents, boronic-acid inhibitor, cyclic diester with glycerol, hydrolase
• Biological source: Zika virus (ZIKV); More
• Cellular location: Virion membrane ; Multi-pass membrane protein : A0A140DLX4
• Total number of polymer chains: 2
• Total formula weight: 49487.00

Authors

Lei, J.,Hansen, G.,Zhang, L.L.,Hilgenfeld, R. (deposition date: 2016-06-18, release date: 2016-07-06, Last modification date: 2024-10-23)

Primary citation

Lei, J.,Hansen, G.,Nitsche, C.,Klein, C.D.,Zhang, L.,Hilgenfeld, R.
Crystal structure of Zika virus NS2B-NS3 protease in complex with a boronate inhibitor.
Science, 353:503-505, 2016

PubMed Abstract: 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 Asp(83) of NS2B; ion-pairing between Asp(83) 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.

PubMed: 27386922
DOI: 10.1126/science.aag2419

Experimental method

X-RAY DIFFRACTION (2.7 Å)