PDB 3PWY deposited: 2010-12-09 modified: 2011-05-18
Title Crystal structure of an extender (SPD28345)-modified human PDK1 complex 2
Authors Arndt, J.W., Cancilla, M.T., Cao, K., Elling, R.A., English, N., Erlanson, D.A., Friedman, J., Hansen, S.K., Hession, C., Joseph, I., Kumaravel, G., Lee, W.C., Lind, K.E., McDowell, R.S., Miatkowski, K., Nguyen, C., Nguyen, T.B., Park, S., Pathan, N., Penny, D.M., Romanowski, M.J., Scott, D., Silvian, L., Simmons, R.L., Sun, L., Tangonan, B.T., Yang, W.
Structure factors resolution 3.5 rfactor 0.22014 rfree 0.27649
DPI 2.35 theoretical min: 0.90
Related PDB Entries 3QC4

We report the use of a fragment-based lead discovery method, Tethering with extenders, to discover a pyridinone fragment that binds in an adaptive site of the protein PDK1. With subsequent medicinal chemistry, this led to the discovery of a potent and highly selective inhibitor of PDK1, which binds in the 'DFG-out' conformation.

Bioorg.Med.Chem.Lett. 2011 May; 21(10):3078-3083 doi:10.1016/j.bmcl.2011.03.032

Cross References
Database source Identifier Description
PubMed 21459573 BMCLE8
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
3PWY/0 3PWY 0 monomer 0 1 1 2050