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Friday, 25 September, 2015

Versatile and Efficient Site-Specific Protein Functionalization by Tubulin Tyrosine Ligase

D. Schumacher, J. Helma, F. A. Mann, G. Pichler, F. Natale, E. Krause, C. Cardoso, C. P. R. Hackenberger & H. Leonhardt -
Angew. Chemie Int. Ed. 10.1002/anie.201505456 (2015)

A novel chemoenzymatic approach for simple and fast site-specific protein labeling is reported. Recombinant tubulin tyrosine ligase (TTL) was repurposed to attach various unnatural tyrosine derivatives as small bioorthogonal handles to proteins containing a short tubulin-derived recognition sequence (Tub-tag). This novel strategy enables a broad range of high-yielding and fast chemoselective C-terminal protein modifications on isolated proteins or in cell lysates for applications in biochemistry, cell biology, and beyond, as demonstrated by the site-specific labeling of nanobodies, GFP, and ubiquitin.

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