1q4l: Difference between revisions

Revision as of 05:51, 3 May 2008

GSK-3 Beta complexed with Inhibitor I-5

OverviewOverview

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 StructureAbout this Structure

1Q4L is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 05:51:39 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
 [[Image:1q4l.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1q4l |SIZE=350|CAPTION= <scene name='initialview01'>1q4l</scene>, resolution 2.77&Aring;
+The line below this paragraph, containing "STRUCTURE_1q4l", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=679:2-CHLORO-5-[4-(3-CHLORO-PHENYL)-2,5-DIOXO-2,5-DIHYDRO-1H-PYRROL-3-YLAMINO]-BENZOIC+ACID'>679</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_serine/threonine_protein_kinase Non-specific serine/threonine protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.1 2.7.11.1] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE= GSK3B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+-->
-|DOMAIN=
+{{STRUCTURE_1q4l|  PDB=1q4l  |  SCENE=  }}
-|RELATEDENTRY=[[1pyx|1PYX]], [[1q3d|1Q3D]], [[1q3w|1Q3W]], [[1q41|1Q41]]
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1q4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q4l OCA], [http://www.ebi.ac.uk/pdbsum/1q4l PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1q4l RCSB]</span>
-}}
 '''GSK-3 Beta complexed with Inhibitor I-5'''
@@ Line 34: / Line 31: @@
 [[Category: Valsasina, B.]]
 [[Category: Vulpetti, A.]]
-[[Category: insulin pathway]]
+[[Category: Insulin pathway]]
-[[Category: kinase]]
+[[Category: Kinase]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 05:51:39 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:08:42 2008''