1q41: Difference between revisions
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'''GSK-3 Beta complexed with Indirubin-3'-monoxime''' | '''GSK-3 Beta complexed with Indirubin-3'-monoxime''' | ||
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[[Category: Valsasina, B.]] | [[Category: Valsasina, B.]] | ||
[[Category: Vulpetti, A.]] | [[Category: Vulpetti, A.]] | ||
[[Category: | [[Category: Indirubin-3'-monoxime]] | ||
[[Category: | [[Category: Insulin pathway]] | ||
[[Category: | [[Category: Kinase]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:50:34 2008'' | |||
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Revision as of 02:50, 3 May 2008
GSK-3 Beta complexed with Indirubin-3'-monoxime
Overview
GSK-3beta is a regulatory serine/threonine kinase with a plethora of cellular targets. Consequently, selective small molecule inhibitors of GSK-3beta may have a variety of therapeutic uses including the treatment of neurodegenerative diseases, type II diabetes and cancer. In order to characterize the active site of GSK-3beta, we determined crystal structures of unphosphorylated GSK-3beta in complex with selective and non-selective ATP-mimetic inhibitors. Analysis of the inhibitors' interactions with GSK-3beta in the structures reveals how the enzyme can accommodate a number of diverse molecular scaffolds. In addition, a conserved water molecule near Thr138 is identified that can serve a functional role in inhibitor binding. Finally, a comparison of the interactions made by selective and non-selective inhibitors highlights residues on the edge of the ATP binding-site that can be used to obtain inhibitor selectivity. Information gained from these structures provides a promising route for the design of second-generation GSK-3beta inhibitors.
About this Structure
1Q41 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural characterization of the GSK-3beta active site using selective and non-selective ATP-mimetic inhibitors., Bertrand JA, Thieffine S, Vulpetti A, Cristiani C, Valsasina B, Knapp S, Kalisz HM, Flocco M, J Mol Biol. 2003 Oct 17;333(2):393-407. PMID:14529625 Page seeded by OCA on Sat May 3 05:50:34 2008
