Glycogen synthase kinase 3
From Proteopedia
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== Structure of Anticancer Ruthenium Half-Sandwich Complex Bound to Glycogen Synthase Kinase 3ß <ref>DOI 10.1007/s00775-010-0699-x</ref> == | == Structure of Anticancer Ruthenium Half-Sandwich Complex Bound to Glycogen Synthase Kinase 3ß <ref>DOI 10.1007/s00775-010-0699-x</ref> == | ||
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 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 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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| + | ===3D structures of glycogen synthase kinase 3=== | ||
| + | [[Glycogen synthase kinase 3 3D structures]] | ||
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</StructureSection> | </StructureSection> | ||
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**[[1gng]] - hGSK-3 β + Frattide peptide<br /> | **[[1gng]] - hGSK-3 β + Frattide peptide<br /> | ||
| - | **[[1q4l]], [[1uv5]], [[1q5k]], [[1r0e]], [[2o5k]], [[2ow3]], [[3du8]], [[3f7z]], [[3f88]], [[3i4b]], [[3gb2]], [[3l1s]], [[3q3b]], [[3zrk]], [[3zrl]], [[3zrm]], [[3sd0]], [[4dit]], [[4afj]], [[4acc]], [[4acd]], [[4acg]], [[4ach]], [[3say]], [[4iq6]], [[4j1r]], [[4j71]], [[5k5n]], [[5hlp]], [[5hln]], [[5f94]], [[5f95]], [[5kpk]], [[5kpl]], [[5kpm]] - hGSK-3 β + inhibitor<br /> | + | **[[1q4l]], [[1uv5]], [[1q5k]], [[1r0e]], [[2o5k]], [[2ow3]], [[3du8]], [[3f7z]], [[3f88]], [[3i4b]], [[3gb2]], [[3l1s]], [[3q3b]], [[3zrk]], [[3zrl]], [[3zrm]], [[3sd0]], [[4dit]], [[4afj]], [[4acc]], [[4acd]], [[4acg]], [[4ach]], [[3say]], [[4iq6]], [[4j1r]], [[4j71]], [[5k5n]], [[5hlp]], [[5hln]], [[5f94]], [[5f95]], [[5kpk]], [[5kpl]], [[5kpm]], [[6gjo]], [[6gn1]], [[6h0u]] - hGSK-3 β + inhibitor<br /> |
**[[5t31]] - hGSK-3 β (mutant) + inhibitor<br /> | **[[5t31]] - hGSK-3 β (mutant) + inhibitor<br /> | ||
**[[1pyx]], [[1j1b]] - hGSK-3 β + AMPPNP<br /> | **[[1pyx]], [[1j1b]] - hGSK-3 β + AMPPNP<br /> | ||
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**[[3m1s]], [[3pup]] - hGSK-3 β + Ru complex<br /> | **[[3m1s]], [[3pup]] - hGSK-3 β + Ru complex<br /> | ||
**[[4nm0]], [[4nm3]], [[4nu1]], [[1o9u]], [[4b7t]] - hGSK-3 β + Axin peptide<br /> | **[[4nm0]], [[4nm3]], [[4nu1]], [[1o9u]], [[4b7t]] - hGSK-3 β + Axin peptide<br /> | ||
| + | **[[6ae3]] - GSK-3 β + morin - mouse<br /> | ||
*GSK-3 ternary complex | *GSK-3 ternary complex | ||
Revision as of 08:57, 15 July 2019
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3D structures of glycogen synthase kinase 3
Updated on 15-July-2019
References
- ↑ Forde JE, Dale TC. Glycogen synthase kinase 3: a key regulator of cellular fate. Cell Mol Life Sci. 2007 Aug;64(15):1930-44. PMID:17530463 doi:http://dx.doi.org/10.1007/s00018-007-7045-7
- ↑ Jope RS, Roh MS. Glycogen synthase kinase-3 (GSK3) in psychiatric diseases and therapeutic interventions. Curr Drug Targets. 2006 Nov;7(11):1421-34. PMID:17100582
- ↑ Atilla-Gokcumen GE, Di Costanzo L, Meggers E. Structure of anticancer ruthenium half-sandwich complex bound to glycogen synthase kinase 3beta. J Biol Inorg Chem. 2010 Sep 7. PMID:20821241 doi:10.1007/s00775-010-0699-x
