1okz

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[[Image:1okz.png|left|200px]]
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==STRUCTURE OF HUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH UCN-01==
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<StructureSection load='1okz' size='340' side='right' caption='[[1okz]], [[Resolution|resolution]] 2.51&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1okz]] is a 1 chain structure with 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=1OKZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1OKZ FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UCN:7-HYDROXYSTAUROSPORINE'>UCN</scene><br>
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<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1h1w|1h1w]], [[1oky|1oky]], [[1uu3|1uu3]], [[1uu7|1uu7]], [[1uu8|1uu8]], [[1uu9|1uu9]], [[1uvr|1uvr]]</td></tr>
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<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1okz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1okz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1okz RCSB], [http://www.ebi.ac.uk/pdbsum/1okz PDBsum]</span></td></tr>
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<table>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ok/1okz_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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PDK1 (3-phosphoinositide-dependent protein kinase-1) is a member of the AGC (cAMP-dependent, cGMP-dependent, protein kinase C) family of protein kinases, and has a key role in insulin and growth-factor signalling through phosphorylation and subsequent activation of a number of other AGC kinase family members, such as protein kinase B. The staurosporine derivative UCN-01 (7-hydroxystaurosporine) has been reported to be a potent inhibitor for PDK1, and is currently undergoing clinical trials for the treatment of cancer. Here, we report the crystal structures of staurosporine and UCN-01 in complex with the kinase domain of PDK1. We show that, although staurosporine and UCN-01 interact with the PDK1 active site in an overall similar manner, the UCN-01 7-hydroxy group, which is not present in staurosporine, generates direct and water-mediated hydrogen bonds with active-site residues. Inhibition data from UCN-01 tested against a panel of 29 different kinases show a different pattern of inhibition compared with staurosporine. We discuss how these differences in inhibition could be attributed to specific interactions with the additional 7-hydroxy group, as well as the size of the 7-hydroxy-group-binding pocket. This information could lead to opportunities for structure-based optimization of PDK1 inhibitors.
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{{STRUCTURE_1okz| PDB=1okz | SCENE= }}
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Structural basis for UCN-01 (7-hydroxystaurosporine) specificity and PDK1 (3-phosphoinositide-dependent protein kinase-1) inhibition.,Komander D, Kular GS, Bain J, Elliott M, Alessi DR, Van Aalten DM Biochem J. 2003 Oct 15;375(Pt 2):255-62. PMID:12892559<ref>PMID:12892559</ref>
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===STRUCTURE OF HUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH UCN-01===
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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{{ABSTRACT_PUBMED_12892559}}
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==See Also==
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*[[3-phosphoinositide-dependent protein kinase 1|3-phosphoinositide-dependent protein kinase 1]]
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==About this Structure==
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== References ==
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[[1okz]] is a 1 chain structure with 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=1OKZ OCA].
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<references/>
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__TOC__
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==Reference==
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</StructureSection>
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<ref group="xtra">PMID:012892559</ref><references group="xtra"/>
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]

Revision as of 16:47, 28 September 2014

STRUCTURE OF HUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH UCN-01

1okz, resolution 2.51Å

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