Journal:JBIC:2
From Proteopedia
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| - | <applet load="" size="600" color="" frame="true" spin="on" Scene ="Journal:JBIC:2/ | + | <applet load="" size="600" color="" frame="true" spin="on" Scene ="Journal:JBIC:2/Opening/1" align="right" caption="Crystal Structure of Glycogen Synthase Kinase 3ß bound to Anticancer Ruthenium Complex "/> |
===Structure of Anticancer Ruthenium Half-Sandwich Complex Bound to Glycogen Synthase Kinase 3ß=== | ===Structure of Anticancer Ruthenium Half-Sandwich Complex Bound to Glycogen Synthase Kinase 3ß=== | ||
<big>G. Atilla-Gocumen, L. Di Costanzo, E. Meggers</big> | <big>G. Atilla-Gocumen, L. Di Costanzo, E. Meggers</big> | ||
Revision as of 10:20, 25 August 2010
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Structure of Anticancer Ruthenium Half-Sandwich Complex Bound to Glycogen Synthase Kinase 3ß
G. Atilla-Gocumen, L. Di Costanzo, E. Meggers
A crystal structure of an bound to the protein kinase glycogen synthase kinase 3ß (GSK-3ß) has been determined and reveals the binding to via an induced fit mechanism utlizing several and (Click: ). Importantly, the metal is not involved in any direct interaction with the protein kinase but fulfills a purely structural role. The unique, bulky molecular structure of the half-sandwich complex 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. Although this complex is a conventional ATP-competitive binder, the unique shape of the complex allows novel interactions with the glycine-rich loop which are crucial for binding potency and selectivity. It can be hypothesized that coordination spheres which present other ligands towards the glycine-rich loop might display completely different protein kinase selectivities.
