3M1S

Structure of Ruthenium Half-Sandwich Complex Bound to Glycogen Synthase Kinase 3

Summary for 3M1S

• Entry DOI: 10.2210/pdb3m1s/pdb
• Descriptor: Glycogen synthase kinase-3 beta, Ruthenium pyridocarbazole (3 entities in total)
• Functional Keywords: transferase, enzyme inhibitor, organometallic compound, ruthenium center, ruthenium pyridocarbazole, atp-binding, kinase, phosphoprotein, serine/threonine-protein kinase, wnt signaling pathway, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P49841
• Total number of polymer chains: 2
• Total formula weight: 94595.30

Authors

Atilla-Gokcumen, G.E.,Di Costanzo, L.,Zimmermann, G.,Meggers, E. (deposition date: 2010-03-05, release date: 2010-12-22, Last modification date: 2023-09-06)

Primary citation

Atilla-Gokcumen, G.E.,Di Costanzo, L.,Meggers, E.
Structure of anticancer ruthenium half-sandwich complex bound to glycogen synthase kinase 3beta
J.Biol.Inorg.Chem., 16:45-50, 2011

PubMed Abstract: The 3.15-Å-resolution crystal structure of the R enantiomer of the highly bioactive and antiproliferative half-sandwich ruthenium complex DW12 bound to the ATP binding site of glycogen synthase kinase 3β (GSK-3β) is reported and the binding is compared with the GSK-3β binding of staurosporine and other organic inhibitors. The structure reveals a close packing of the organometallic inhibitor in the ATP binding site of GSK-3β via an induced-fit mechanism. The molecular structure of (R)-DW12 with the CO ligand oriented perpendicular to the pyridocarbazole heterocycle allows the complex to stretch the whole distance sandwiched between the faces of the N- and C-terminal lobes and to interact tightly with the flexible glycine-rich loop, which is uncommon for the interaction of GSK-3β with organic inhibitors.

PubMed: 20821241
DOI: 10.1007/s00775-010-0699-x

Experimental method

X-RAY DIFFRACTION (3.134 Å)