1uv5

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[[Image:1uv5.gif|left|200px]]
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{{Seed}}
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[[Image:1uv5.png|left|200px]]
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{{STRUCTURE_1uv5| PDB=1uv5 | SCENE= }}
{{STRUCTURE_1uv5| PDB=1uv5 | SCENE= }}
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'''GLYCOGEN SYNTHASE KINASE 3 BETA COMPLEXED WITH 6-BROMOINDIRUBIN-3'-OXIME'''
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===GLYCOGEN SYNTHASE KINASE 3 BETA COMPLEXED WITH 6-BROMOINDIRUBIN-3'-OXIME===
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==Overview==
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Gastropod mollusks have been used for over 2500 years to produce the "Tyrian purple" dye made famous by the Phoenicians. This dye is constituted of mixed bromine-substituted indigo and indirubin isomers. Among these, the new natural product 6-bromoindirubin and its synthetic, cell-permeable derivative, 6-bromoindirubin-3'-oxime (BIO), display remarkable selective inhibition of glycogen synthase kinase-3 (GSK-3). Cocrystal structure of GSK-3beta/BIO and CDK5/p25/indirubin-3'-oxime were resolved, providing a detailed view of indirubins' interactions within the ATP binding pocket of these kinases. BIO but not 1-methyl-BIO, its kinase inactive analog, also inhibited the phosphorylation on Tyr276/216, a GSK-3alpha/beta activation site. BIO but not 1-methyl-BIO reduced beta-catenin phosphorylation on a GSK-3-specific site in cellular models. BIO but not 1-methyl-BIO closely mimicked Wnt signaling in Xenopus embryos. 6-bromoindirubins thus provide a new scaffold for the development of selective and potent pharmacological inhibitors of GSK-3.
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(as it appears on PubMed at http://www.pubmed.gov), where 14700633 is the PubMed ID number.
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{{ABSTRACT_PUBMED_14700633}}
==About this Structure==
==About this Structure==
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[[Category: Transferase serine/threonine-protein kinase]]
[[Category: Transferase serine/threonine-protein kinase]]
[[Category: Wnt signaling pathway]]
[[Category: Wnt signaling pathway]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 11:43:57 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 14:00:52 2008''

Revision as of 11:00, 29 July 2008

Image:1uv5.png

Template:STRUCTURE 1uv5

GLYCOGEN SYNTHASE KINASE 3 BETA COMPLEXED WITH 6-BROMOINDIRUBIN-3'-OXIME

Template:ABSTRACT PUBMED 14700633

About this Structure

1UV5 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

GSK-3-selective inhibitors derived from Tyrian purple indirubins., Meijer L, Skaltsounis AL, Magiatis P, Polychronopoulos P, Knockaert M, Leost M, Ryan XP, Vonica CA, Brivanlou A, Dajani R, Crovace C, Tarricone C, Musacchio A, Roe SM, Pearl L, Greengard P, Chem Biol. 2003 Dec;10(12):1255-66. PMID:14700633

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