The structure of a NEMO construct engineered for screening reveals novel determinants of inhibition

What is it about?

In this work we tried to develop a construct of the IKK-binding domain of NEMO that would facilitate structure determination and NMR-based inhibitor screening and validation. That was possible by optimizing with "surgical precision" single residues that would stabilize the structure while maintaining wildtype-like folding and IKKbeta-binding. That is zipNEMO!

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Why is it important?

zipNEMO enables drug discovery techniques essential for developing inhibitors of protein-protein interaction (here NEMO and IKKbeta), like 1H,15N HSQC NMR and X-ray crystallography. We will be able to determine where the inhibitors bind and how they bind, facilitating the optimization process.