3KWI

X-ray structure of NS1 effector domain W187Y mutant

Summary for 3KWI

• Entry DOI: 10.2210/pdb3kwi/pdb
• Related: 3EE8 3EE9 3KWG
• Descriptor: Non-structural protein 1 (2 entities in total)
• Functional Keywords: influenza, ns1, effector domain, alternative splicing, host cytoplasm, host nucleus, host-virus interaction, interferon antiviral system evasion, rna-binding, suppressor of rna silencing, viral protein
• Biological source: Influenza A virus
• Cellular location: Host nucleus: P03495
• Total number of polymer chains: 2
• Total formula weight: 32028.85

Authors

Xia, S.,Robertus, J.D. (deposition date: 2009-12-01, release date: 2010-02-02, Last modification date: 2023-09-06)

Primary citation

Xia, S.,Robertus, J.D.
X-ray structures of NS1 effector domain mutants.
Arch.Biochem.Biophys., 494:198-204, 2010

PubMed Abstract: The influenza A virus nonstructural protein NS1 is a multifunctional dimeric protein that acts as a potent inhibitor of the host cellular antiviral state. The C-terminal effector domain of NS1 binds host proteins, including CPSF30, and is a target for the development of new antiviral drugs. Here we present crystallographic structures of two mutant effector domains, W187Y and W187A, of influenza A/Udorn/72 virus. Unlike wild-type, the mutants behave exclusively as monomers in solution based on gel filtration data and light scattering. The W187Y mutant is able to bind CPSF30 with a binding affinity close to the wild-type protein; that is, it retains a receptor site for aromatic ligands nearly identical to the wild-type. Therefore, this monomeric mutant protein could serve as a drug target for a high throughput inhibitor screening assays, since its binding pocket is unoccupied in solution and potentially more accessible to small molecule ligands.

PubMed: 19995550
DOI: 10.1016/j.abb.2009.12.008

Experimental method

X-RAY DIFFRACTION (2.21 Å)