Journal:JBIC:2
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<b>Molecular Tour</b><br> | <b>Molecular Tour</b><br> | ||
A crystal structure of an <scene name='Journal:JBIC:2/Half_sandwich_complex_no_bonds/1'>organometallic half-sandwich ruthenium complex</scene> bound to the protein kinase glycogen synthase kinase 3ß (GSK-3ß) has been determined (PDB entry [[3m1s]]) and reveals that the inhibitor binds to the <scene name='Journal:JBIC:2/Atp_binding_site2/2'>ATP binding site</scene> via an induced fit mechanism utlizing several <scene name='Journal:JBIC:2/Half_sandwich_complex/3'>hydrogen bonds</scene> and <scene name='Journal:JBIC:2/Half_sandwich_hydrophobic_stic/1'>hydrophobic interactions</scene>. 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 <scene name='Journal:JBIC:2/Half_sandwich_hydrophobic/5'>sandwiched between the faces of the N- and C-terminal lobes</scene> and to interact tightly with <scene name='Journal:JBIC:2/Glycine_rich_loop2/4'>the flexible glycine-rich loop</scene>. 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. | A crystal structure of an <scene name='Journal:JBIC:2/Half_sandwich_complex_no_bonds/1'>organometallic half-sandwich ruthenium complex</scene> bound to the protein kinase glycogen synthase kinase 3ß (GSK-3ß) has been determined (PDB entry [[3m1s]]) and reveals that the inhibitor binds to the <scene name='Journal:JBIC:2/Atp_binding_site2/2'>ATP binding site</scene> via an induced fit mechanism utlizing several <scene name='Journal:JBIC:2/Half_sandwich_complex/3'>hydrogen bonds</scene> and <scene name='Journal:JBIC:2/Half_sandwich_hydrophobic_stic/1'>hydrophobic interactions</scene>. 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 <scene name='Journal:JBIC:2/Half_sandwich_hydrophobic/5'>sandwiched between the faces of the N- and C-terminal lobes</scene> and to interact tightly with <scene name='Journal:JBIC:2/Glycine_rich_loop2/4'>the flexible glycine-rich loop</scene>. 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. | ||
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| + | '''PDB reference:''' Structure of Ruthenium Half-Sandwich Complex Bound to Glycogen Synthase Kinase 3, [[3m1s]]. | ||
<b>References</b><br> | <b>References</b><br> | ||
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This page complements a publication in scientific journals and is one of the Proteopedia's Interactive 3D Complement pages. For aditional details please see I3DC.
