3IW4

Crystal structure of PKC alpha in complex with NVP-AEB071

Summary for 3IW4

• Entry DOI: 10.2210/pdb3iw4/pdb
• Descriptor: Protein kinase C alpha type, 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]-1H-pyrrole-2,5-dione (3 entities in total)
• Functional Keywords: kinase, atp-binding, cell membrane, membrane, metal-binding, nucleotide-binding, phorbol-ester binding, phosphoprotein, serine/threonine-protein kinase, transferase, zinc-finger
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P17252
• Total number of polymer chains: 3
• Total formula weight: 126029.60

Authors

Stark, W.,Rummel, G.,Strauss, A.,Cowan-Jacob, S.W. (deposition date: 2009-09-02, release date: 2009-11-03, Last modification date: 2024-11-20)

Primary citation

Wagner, J.,von Matt, P.,Sedrani, R.,Albert, R.,Cooke, N.,Ehrhardt, C.,Geiser, M.,Rummel, G.,Stark, W.,Strauss, A.,Cowan-Jacob, S.W.,Beerli, C.,Weckbecker, G.,Evenou, J.P.,Zenke, G.,Cottens, S.
Discovery of 3-(1H-indol-3-yl)-4-[2-(4-methylpiperazin-1-yl)quinazolin-4-yl]pyrrole-2,5-dione (AEB071), a potent and selective inhibitor of protein kinase C isotypes
J.Med.Chem., 52:6193-6196, 2009

PubMed Abstract: A series of novel maleimide-based inhibitors of protein kinase C (PKC) were designed, synthesized, and evaluated. AEB071 (1) was found to be a potent, selective inhibitor of classical and novel PKC isotypes. 1 is a highly efficient immunomodulator, acting via inhibition of early T cell activation. The binding mode of maleimides to PKCs, proposed by molecular modeling, was confirmed by X-ray analysis of 1 bound in the active site of PKCalpha.

PubMed: 19827831
DOI: 10.1021/jm901108b

Experimental method

X-RAY DIFFRACTION (2.8 Å)