3PWY

Crystal structure of an extender (SPD28345)-modified human PDK1 complex 2

Summary for 3PWY

• Entry DOI: 10.2210/pdb3pwy/pdb
• Descriptor: 3-phosphoinositide-dependent protein kinase 1, N-[2-({6-[(2-sulfanylethyl)amino]pyrimidin-4-yl}amino)ethyl]propanamide (2 entities in total)
• Functional Keywords: kinase, fragment-based drug discovery, tethering with extenders, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: O15530
• Total number of polymer chains: 1
• Total formula weight: 35729.13

Authors

Elling, R.A.,Penny, D.M.,Simmons, R.L.,Erlanson, D.A.,Romanowski, M.J. (deposition date: 2010-12-09, release date: 2011-04-20, Last modification date: 2024-10-09)

Primary citation

Erlanson, D.A.,Arndt, J.W.,Cancilla, M.T.,Cao, K.,Elling, R.A.,English, N.,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.,Tangonan, B.T.,Yang, W.,Sun, L.
Discovery of a potent and highly selective PDK1 inhibitor via fragment-based drug discovery.
Bioorg.Med.Chem.Lett., 21:3078-3083, 2011

PubMed Abstract: 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.

PubMed: 21459573
DOI: 10.1016/j.bmcl.2011.03.032

Experimental method

X-RAY DIFFRACTION (3.5 Å)