3FXZ

Crystal structure of PAK1 kinase domain with ruthenium complex lambda-FL172

Summary for 3FXZ

• Entry DOI: 10.2210/pdb3fxz/pdb
• Related: 3FY0
• Descriptor: Serine/threonine-protein kinase PAK 1, OCTAHEDRAL RU-PYRIDOCARBAZOLE (3 entities in total)
• Functional Keywords: transferase, kinase, atp-binding, phosphorylation, allosteric enzyme, alternative splicing, apoptosis, cell junction, cytoplasm, nucleotide-binding, phosphoprotein, polymorphism, serine/threonine-protein kinase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: Q13153
• Total number of polymer chains: 1
• Total formula weight: 34035.26

Authors

Maksimoska, J.,Marmorstein, R.,Meggers, E. (deposition date: 2009-01-21, release date: 2009-02-17, Last modification date: 2024-11-27)

Primary citation

Maksimoska, J.,Feng, L.,Harms, K.,Yi, C.,Kissil, J.,Marmorstein, R.,Meggers, E.
Targeting Large Kinase Active Site with Rigid, Bulky Octahedral Ruthenium Complexes
J.Am.Chem.Soc., 130:15764-15765, 2008

PubMed Abstract: A strategy for targeting protein kinases with large ATP-binding sites by using bulky and rigid octahedral ruthenium complexes as structural scaffolds is presented. A highly potent and selective GSK3 and Pim1 half-sandwich complex NP309 was successfully converted into a PAK1 inhibitor by making use of the large octahedral compounds Lambda-FL172 and Lambda-FL411 in which the cyclopentadienyl moiety of NP309 is replaced by a chloride and sterically demanding diimine ligands. A 1.65 A cocrystal structure of PAK1 with Lambda-FL172 reveals how the large coordination sphere of the ruthenium complex matches the size of the active site and serves as a yardstick to discriminate between otherwise closely related binding sites.

PubMed: 18973295

Experimental method

X-RAY DIFFRACTION (1.64 Å)