2io6

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[[Image:2io6.jpg|left|200px]]
[[Image:2io6.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 2io6 |SIZE=350|CAPTION= <scene name='initialview01'>2io6</scene>, resolution 2.20&Aring;
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The line below this paragraph, containing "STRUCTURE_2io6", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=330:9-HYDROXY-6-(3-HYDROXYPROPYL)-4-(2-METHOXYPHENYL)PYRROLO[3,4-C]CARBAZOLE-1,3(2H,6H)-DIONE'>330</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Non-specific_protein-tyrosine_kinase Non-specific protein-tyrosine kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.10.2 2.7.10.2] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE= WEE1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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-->
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|DOMAIN=
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{{STRUCTURE_2io6| PDB=2io6 | SCENE= }}
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|RELATEDENTRY=[[1x8b|1X8B]], [[2in6|2IN6]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2io6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2io6 OCA], [http://www.ebi.ac.uk/pdbsum/2io6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2io6 RCSB]</span>
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}}
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'''Wee1 kinase complexed with inhibitor PD330961'''
'''Wee1 kinase complexed with inhibitor PD330961'''
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[[Category: Ivanovic, I.]]
[[Category: Ivanovic, I.]]
[[Category: Squire, C J.]]
[[Category: Squire, C J.]]
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[[Category: protein-inhibitor complex]]
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[[Category: Protein-inhibitor complex]]
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[[Category: transferase]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:42:42 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:46:44 2008''
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Revision as of 04:42, 4 May 2008

Template:STRUCTURE 2io6

Wee1 kinase complexed with inhibitor PD330961


Overview

A series of N-6 substituted 9-hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones were prepared from N-substituted (5-methoxyphenyl)ethenylindoles. The target compounds were tested for their ability to inhibit the G2/M cell cycle checkpoint kinases, Wee1 and Chk1. Analogues with neutral or cationic N-6 side chains were potent dual inhibitors. Acidic side chains provided potent (average IC(50) 0.057muM) and selective (average ratio 223-fold) Wee1 inhibition. Co-crystal structures of inhibitors bound to Wee1 show that the pyrrolo[3,4-c]carbazole scaffold binds in the ATP-binding site, with N-6 substituents involved in H-bonding to conserved water molecules. HT-29 cells treated with doxorubicin and then target compounds demonstrate an active Cdc2/cyclin B complex, inhibition of the doxorubicin-induced phosphorylation of tyrosine 15 of Cdc2 and abrogation of the G2 checkpoint.

About this Structure

2IO6 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Synthesis and structure-activity relationships of N-6 substituted analogues of 9-hydroxy-4-phenylpyrrolo[3,4-c]carbazole-1,3(2H,6H)-diones as inhibitors of Wee1 and Chk1 checkpoint kinases., Smaill JB, Baker EN, Booth RJ, Bridges AJ, Dickson JM, Dobrusin EM, Ivanovic I, Kraker AJ, Lee HH, Lunney EA, Ortwine DF, Palmer BD, Quin J 3rd, Squire CJ, Thompson AM, Denny WA, Eur J Med Chem. 2007 Aug 6;. PMID:17869387 Page seeded by OCA on Sun May 4 07:42:42 2008

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