2C1B

Structure of cAMP-dependent protein kinase complexed with (4R,2S)-5'-(4-(4-Chlorobenzyloxy)pyrrolidin-2-ylmethanesulfonyl)isoquinoline

Summary for 2C1B

• Entry DOI: 10.2210/pdb2c1b/pdb
• Related: 1CMK 1KMU 1KMW 1Q24 1Q61 1Q62 1Q8T 1Q8U 1Q8W 1SMH 1STC 1SVE 1SVG 1SVH 1SZM 1VEB 1YDR 1YDS 1YDT 2C1A
• Descriptor: CAMP-DEPENDENT PROTEIN KINASE, CAMP-DEPENDENT PROTEIN KINASE INHIBITOR, (4R,2S)-5'-(4-(4-CHLOROBENZYLOXY)PYRROLIDIN-2-YLMETHANESULFONYL)ISOQUINOLINE, ... (4 entities in total)
• Functional Keywords: transferase/inhibitor, complex (transferase-inhibitor), atp-binding, camp, phosphorylation, transferase, serine/threonine-protein kinase, protein kinase inhibitor, transferase-inhibitor complex
• Biological source: BOS TAURUS; More
• Cellular location: Cytoplasm : P00517
• Total number of polymer chains: 2
• Total formula weight: 43495.96

Authors

Collins, I.,Caldwell, J.,Fonseca, T.,Donald, A.,Bavetsias, V.,Hunter, L.J.,Garrett, M.D.,Rowlands, M.G.,Aherne, G.W.,Davies, T.G.,Berdini, V.,Woodhead, S.J.,Seavers, L.C.A.,Wyatt, P.G.,Workman, P.,McDonald, E. (deposition date: 2005-09-12, release date: 2005-11-02, Last modification date: 2024-10-16)

Primary citation

Collins, I.,Caldwell, J.,Fonseca, T.,Donald, A.,Bavetsias, V.,Hunter, L.J.,Garrett, M.D.,Rowlands, M.G.,Aherne, G.W.,Davies, T.G.,Berdini, V.,Woodhead, S.J.,Davis, D.,Seavers, L.C.,Wyatt, P.G.,Workman, P.,McDonald, E.
Structure-based design of isoquinoline-5-sulfonamide inhibitors of protein kinase B.
Bioorg. Med. Chem., 14:1255-1273, 2006

PubMed Abstract: Structure-based drug design of novel isoquinoline-5-sulfonamide inhibitors of PKB as potential antitumour agents was investigated. Constrained pyrrolidine analogues that mimicked the bound conformation of linear prototypes were identified and investigated by co-crystal structure determinations with the related protein PKA. Detailed variation in the binding modes between inhibitors with similar overall conformations was observed. Potent PKB inhibitors from this series inhibited GSK3beta phosphorylation in cellular assays, consistent with inhibition of PKB kinase activity in cells.

PubMed: 16249095
DOI: 10.1016/j.bmc.2005.09.055

Experimental method

X-RAY DIFFRACTION (2 Å)