Investigating protein-ligand interactions with a mutant FKBP possessing a designed specificity pocket.

@article{Yang2000InvestigatingPI,
  title={Investigating protein-ligand interactions with a mutant FKBP possessing a designed specificity pocket.},
  author={Wu Yang and Leonard W Rozamus and Satwant K. Narula and Carl T Rollins and R D Yuan and Lu{\'i}s Jesu{\'i}no de Oliveira Andrade and M. Kalyan Ram and Thomas B. Phillips and Marie Rose van Schravendijk and David C Dalgarno and Tim Clackson and Dennis A. Holt},
  journal={Journal of medicinal chemistry},
  year={2000},
  volume={43 6},
  pages={1135-42}
}
Using structure-based design and protein mutagenesis we have remodeled the FKBP12 ligand binding site to include a sizable, hydrophobic specificity pocket. This mutant (F36V-FKBP) is capable of binding, with low or subnanomolar affinities, novel synthetic ligands possessing designed substituents that sterically prevent binding to the wild-type protein. Using binding and structural analysis of bumped compounds, we show here that the pocket is highly promiscuous-capable of binding a range of… CONTINUE READING