Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

We developed a 'computational second-site suppressor' strategy to redesign specificity at a protein-protein interface and applied it to create new specifically interacting DNase-inhibitor protein pairs. We demonstrate that the designed switch in specificity holds in in vitro binding and functional assays. We also show that the designed interfaces are specific in the natural functional context in living cells, and present the first high-resolution X-ray crystallographic analysis of a computer-redesigned functional protein-protein interface with altered specificity. The approach should be applicable to the design of interacting protein pairs with novel specificities for delineating and re-engineering protein interaction networks in living cells.

Original publication

DOI

10.1038/nsmb749

Type

Journal article

Journal

Nat Struct Mol Biol

Publication Date

04/2004

Volume

11

Pages

371 - 379

Keywords

Bacterial Proteins, Binding Sites, Computational Biology, Deoxyribonucleases, Kinetics, Models, Molecular, Protein Structure, Secondary, Proteins, Sensitivity and Specificity