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Publication Abstract from PubMed

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.

X-ray structures of NS1 effector domain mutants.,Xia S, Robertus JD Arch Biochem Biophys. 2010 Feb 15;494(2):198-204. Epub 2009 Dec 6. PMID:19995550^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.