1PYX
GSK-3 Beta complexed with AMP-PNP
Summary for 1PYX
| Entry DOI | 10.2210/pdb1pyx/pdb |
| Descriptor | Glycogen synthase kinase-3 beta, MAGNESIUM ION, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, ... (4 entities in total) |
| Functional Keywords | kinase, insulin pathway, transferase |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm: P49841 |
| Total number of polymer chains | 2 |
| Total formula weight | 95020.38 |
| Authors | Bertrand, J.A.,Thieffine, S.,Vulpetti, A.,Cristiani, C.,Valsasina, B.,Knapp, S.,Kalisz, H.M.,Flocco, M. (deposition date: 2003-07-09, release date: 2003-10-21, Last modification date: 2023-08-16) |
| Primary citation | Bertrand, J.A.,Thieffine, S.,Vulpetti, A.,Cristiani, C.,Valsasina, B.,Knapp, S.,Kalisz, H.M.,Flocco, M. Structural characterization of the GSK-3beta active site using selective and non-selective ATP-mimetic inhibitors J.Mol.Biol., 333:393-407, 2003 Cited by PubMed Abstract: 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. PubMed: 14529625DOI: 10.1016/j.jmb.2003.08.031 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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