1pyx: Difference between revisions

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Revision as of 14:30, 20 March 2008

File:1pyx.gif

, resolution 2.40Å

Ligands:

and

Gene:

GSK3B (Homo sapiens)

Activity:

Non-specific serine/threonine protein kinase, with EC number 2.7.11.1

Coordinates:

save as pdb, mmCIF, xml

GSK-3 Beta complexed with AMP-PNP

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

1PYX 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 Thu Mar 20 13:30:47 2008

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

OCA

@@ Line 1: / Line 1: @@
-[[Image:1pyx.gif|left|200px]]<br /><applet load="1pyx" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:1pyx.gif|left|200px]]
-caption="1pyx, resolution 2.40&Aring;" />
-'''GSK-3 Beta complexed with AMP-PNP'''<br />
+ {{Structure
+|PDB= 1pyx |SIZE=350|CAPTION= <scene name='initialview01'>1pyx</scene>, resolution 2.40&Aring;
+|SITE=
+|LIGAND= <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene> and <scene name='pdbligand=ANP:PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER'>ANP</scene>
+|ACTIVITY= [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]
+|GENE= GSK3B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
+}}
+'''GSK-3 Beta complexed with AMP-PNP'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-PYX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=ANP:'>ANP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PYX OCA].
+PYX is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PYX 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14529625 14529625]
+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:[http://www.ncbi.nlm.nih.gov/pubmed/14529625 14529625]
 [[Category: Homo sapiens]]
 [[Category: Non-specific serine/threonine protein kinase]]
@@ Line 27: / Line 36: @@
 [[Category: kinase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:34:01 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:30:47 2008''