1uu3: Difference between revisions

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[[Image:1uu3.png|left|200px]]
==STRUCTURE OF HUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH LY333531==
<StructureSection load='1uu3' size='340' side='right' caption='[[1uu3]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1uu3]] 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=1UU3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1UU3 FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=LY4:(9R)-9-[(DIMETHYLAMINO)METHYL]-6,7,10,11-TETRAHYDRO-9H,18H-5,21 12,17-DIMETHENODIBENZO[E,K]PYRROLO[3,4-H][1,4,13]OXADIAZACYCLOHEXADECINE-18,20-DIONE'>LY4</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
<tr><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1h1w|1h1w]], [[1oky|1oky]], [[1okz|1okz]], [[1uu7|1uu7]], [[1uu8|1uu8]], [[1uu9|1uu9]], [[1uvr|1uvr]]</td></tr>
<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>
<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=1uu3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1uu3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1uu3 RCSB], [http://www.ebi.ac.uk/pdbsum/1uu3 PDBsum]</span></td></tr>
<table>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/uu/1uu3_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
LY333531, BIM-1, BIM-2, BIM-3, and BIM-8 are bisindolyl maleimide-based, nanomolar protein kinase C inhibitors. LY333531, a PKCbeta-specific inhibitor, is in clinical trials against diabetes and cardiac ventricular hypertrophy complications. Specificity analysis with a panel of 29 protein kinases reveals that these bisindolyl maleimide inhibitors also inhibit PDK1, a key kinase from the insulin signaling pathway, albeit in the lower microM range. To understand the molecular basis of inhibition, the PDK1 kinase domain was cocrystallized with these bisindolyl maleimide inhibitors. The inhibitor complexes represent the first structural description of this class of compounds, revealing their unusual nonplanar conformation within the ATP binding site and also explaining the higher inhibitory potential of LY33331 compared to the BIM compounds toward PDK1. A combination of site-directed mutagenesis and essential dynamics analysis gives further insight into PDK1 and also PKC inhibition by these compounds, and may aid inhibitor design.


{{STRUCTURE_1uu3|  PDB=1uu3  |  SCENE=  }}
Interactions of LY333531 and other bisindolyl maleimide inhibitors with PDK1.,Komander D, Kular GS, Schuttelkopf AW, Deak M, Prakash KR, Bain J, Elliott M, Garrido-Franco M, Kozikowski AP, Alessi DR, van Aalten DM Structure. 2004 Feb;12(2):215-26. PMID:14962382<ref>PMID:14962382</ref>


===STRUCTURE OF HUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH LY333531===
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>


{{ABSTRACT_PUBMED_14962382}}
==See Also==
 
*[[3-phosphoinositide-dependent protein kinase 1|3-phosphoinositide-dependent protein kinase 1]]
==About this Structure==
== References ==
[[1uu3]] 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=1UU3 OCA].
<references/>
 
__TOC__
==Reference==
</StructureSection>
<ref group="xtra">PMID:014962382</ref><references group="xtra"/>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Non-specific serine/threonine protein kinase]]
[[Category: Non-specific serine/threonine protein kinase]]

Revision as of 00:44, 30 September 2014

STRUCTURE OF HUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH LY333531STRUCTURE OF HUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH LY333531

Structural highlights

1uu3 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, ,
NonStd Res:
Related:1h1w, 1oky, 1okz, 1uu7, 1uu8, 1uu9, 1uvr
Activity:Non-specific serine/threonine protein kinase, with EC number 2.7.11.1
Resources:FirstGlance, OCA, RCSB, PDBsum

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

LY333531, BIM-1, BIM-2, BIM-3, and BIM-8 are bisindolyl maleimide-based, nanomolar protein kinase C inhibitors. LY333531, a PKCbeta-specific inhibitor, is in clinical trials against diabetes and cardiac ventricular hypertrophy complications. Specificity analysis with a panel of 29 protein kinases reveals that these bisindolyl maleimide inhibitors also inhibit PDK1, a key kinase from the insulin signaling pathway, albeit in the lower microM range. To understand the molecular basis of inhibition, the PDK1 kinase domain was cocrystallized with these bisindolyl maleimide inhibitors. The inhibitor complexes represent the first structural description of this class of compounds, revealing their unusual nonplanar conformation within the ATP binding site and also explaining the higher inhibitory potential of LY33331 compared to the BIM compounds toward PDK1. A combination of site-directed mutagenesis and essential dynamics analysis gives further insight into PDK1 and also PKC inhibition by these compounds, and may aid inhibitor design.

Interactions of LY333531 and other bisindolyl maleimide inhibitors with PDK1.,Komander D, Kular GS, Schuttelkopf AW, Deak M, Prakash KR, Bain J, Elliott M, Garrido-Franco M, Kozikowski AP, Alessi DR, van Aalten DM Structure. 2004 Feb;12(2):215-26. PMID:14962382[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Komander D, Kular GS, Schuttelkopf AW, Deak M, Prakash KR, Bain J, Elliott M, Garrido-Franco M, Kozikowski AP, Alessi DR, van Aalten DM. Interactions of LY333531 and other bisindolyl maleimide inhibitors with PDK1. Structure. 2004 Feb;12(2):215-26. PMID:14962382 doi:10.1016/j.str.2004.01.005

1uu3, resolution 1.70Å

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