1uv5: Difference between revisions

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Revision as of 15:37, 20 March 2008

File:1uv5.gif

, resolution 2.80Å

Sites:

Ligands:

, , and

Activity:

Transferred entry: 2.7.11.1, with EC number 2.7.1.37

Coordinates:

save as pdb, mmCIF, xml

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

OverviewOverview

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.

About this StructureAbout this Structure

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

ReferenceReference

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

Page seeded by OCA on Thu Mar 20 14:37:10 2008

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

OCA

@@ Line 1: / Line 1: @@
-[[Image:1uv5.gif|left|200px]]<br /><applet load="1uv5" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:1uv5.gif|left|200px]]
-caption="1uv5, resolution 2.80&Aring;" />
-'''GLYCOGEN SYNTHASE KINASE 3 BETA COMPLEXED WITH 6-BROMOINDIRUBIN-3'-OXIME'''<br />
+ {{Structure
+|PDB= 1uv5 |SIZE=350|CAPTION= <scene name='initialview01'>1uv5</scene>, resolution 2.80&Aring;
+|SITE= <scene name='pdbsite=AC1:Po4+Binding+Site+For+Chain+A'>AC1</scene>
+|LIGAND= <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene> and <scene name='pdbligand=BRW:6-BROMOINDIRUBIN-3'-OXIME'>BRW</scene>
+|ACTIVITY= [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.1 Transferred entry: 2.7.11.1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.37 2.7.1.37]
+|GENE=
+}}
+'''GLYCOGEN SYNTHASE KINASE 3 BETA COMPLEXED WITH 6-BROMOINDIRUBIN-3'-OXIME'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-UV5 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=PO4:'>PO4</scene>, <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=CO:'>CO</scene> and <scene name='pdbligand=BRW:'>BRW</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.1 Transferred entry: 2.7.11.1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.37 2.7.1.37] Known structural/functional Site: <scene name='pdbsite=AC1:Po4+Binding+Site+For+Chain+A'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UV5 OCA].
+UV5 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=1UV5 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=14700633 14700633]
+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:[http://www.ncbi.nlm.nih.gov/pubmed/14700633 14700633]
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
@@ Line 21: / Line 30: @@
 [[Category: CO]]
 [[Category: PO4]]
-[[Category: insulin pathway ]]
+[[Category: insulin pathway]]
 [[Category: kinase]]
 [[Category: transferase serine/threonine-protein kinase]]
 [[Category: wnt signaling pathway]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:28:40 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:37:10 2008''