1wma

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[[Image:1wma.gif|left|200px]]
[[Image:1wma.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1wma |SIZE=350|CAPTION= <scene name='initialview01'>1wma</scene>, resolution 1.24&Aring;
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The line below this paragraph, containing "STRUCTURE_1wma", 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=AB3:3-(4-AMINO-1-TERT-BUTYL-1H-PYRAZOLO[3,4-D]PYRIMIDIN-3-YL)PHENOL'>AB3</scene>, <scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene>, <scene name='pdbligand=P33:3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL'>P33</scene>, <scene name='pdbligand=PE5:3,6,9,12,15,18,21,24-OCTAOXAHEXACOSAN-1-OL'>PE5</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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/Carbonyl_reductase_(NADPH) Carbonyl reductase (NADPH)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.184 1.1.1.184] </span>
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or leave the SCENE parameter empty for the default display.
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|GENE=
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|DOMAIN=
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{{STRUCTURE_1wma| PDB=1wma | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wma FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wma OCA], [http://www.ebi.ac.uk/pdbsum/1wma PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1wma RCSB]</span>
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}}
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'''Crystal structure of human CBR1 in complex with Hydroxy-PP'''
'''Crystal structure of human CBR1 in complex with Hydroxy-PP'''
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==Reference==
==Reference==
An unbiased cell morphology-based screen for new, biologically active small molecules., Tanaka M, Bateman R, Rauh D, Vaisberg E, Ramachandani S, Zhang C, Hansen KC, Burlingame AL, Trautman JK, Shokat KM, Adams CL, PLoS Biol. 2005 May;3(5):e128. Epub 2005 Apr 5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15799708 15799708]
An unbiased cell morphology-based screen for new, biologically active small molecules., Tanaka M, Bateman R, Rauh D, Vaisberg E, Ramachandani S, Zhang C, Hansen KC, Burlingame AL, Trautman JK, Shokat KM, Adams CL, PLoS Biol. 2005 May;3(5):e128. Epub 2005 Apr 5. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15799708 15799708]
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[[Category: Carbonyl reductase (NADPH)]]
 
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Rauh, D.]]
[[Category: Rauh, D.]]
[[Category: Shokat, K M.]]
[[Category: Shokat, K M.]]
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[[Category: oxidoreductase]]
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[[Category: Oxidoreductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:52:13 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:38:11 2008''
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Revision as of 10:52, 3 May 2008

Image:1wma.gif

Template:STRUCTURE 1wma

Crystal structure of human CBR1 in complex with Hydroxy-PP


Overview

We have implemented an unbiased cell morphology-based screen to identify small-molecule modulators of cellular processes using the Cytometrix (TM) automated imaging and analysis system. This assay format provides unbiased analysis of morphological effects induced by small molecules by capturing phenotypic readouts of most known classes of pharmacological agents and has the potential to read out pathways for which little is known. Four human-cancer cell lines and one noncancerous primary cell type were treated with 107 small molecules comprising four different protein kinase-inhibitor scaffolds. Cellular phenotypes induced by each compound were quantified by multivariate statistical analysis of the morphology, staining intensity, and spatial attributes of the cellular nuclei, microtubules, and Golgi compartments. Principal component analysis was used to identify inhibitors of cellular components not targeted by known protein kinase inhibitors. Here we focus on a hydroxyl-substituted analog (hydroxy-PP) of the known Src-family kinase inhibitor PP2 because it induced cell-specific morphological features distinct from all known kinase inhibitors in the collection. We used affinity purification to identify a target of hydroxy-PP, carbonyl reductase 1 (CBR1), a short-chain dehydrogenase-reductase. We solved the X-ray crystal structure of the CBR1/hydroxy-PP complex to 1.24 A resolution. Structure-based design of more potent and selective CBR1 inhibitors provided probes for analyzing the biological function of CBR1 in A549 cells. These studies revealed a previously unknown function for CBR1 in serum-withdrawal-induced apoptosis. Further studies indicate CBR1 inhibitors may enhance the effectiveness of anticancer anthracyclines. Morphology-based screening of diverse cancer cell types has provided a method for discovering potent new small-molecule probes for cell biological studies and anticancer drug candidates.

About this Structure

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

Reference

An unbiased cell morphology-based screen for new, biologically active small molecules., Tanaka M, Bateman R, Rauh D, Vaisberg E, Ramachandani S, Zhang C, Hansen KC, Burlingame AL, Trautman JK, Shokat KM, Adams CL, PLoS Biol. 2005 May;3(5):e128. Epub 2005 Apr 5. PMID:15799708 Page seeded by OCA on Sat May 3 13:52:13 2008

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