1w1d

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[[Image:1w1d.gif|left|200px]]
[[Image:1w1d.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 1w1d |SIZE=350|CAPTION= <scene name='initialview01'>1w1d</scene>, resolution 1.50&Aring;
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The line below this paragraph, containing "STRUCTURE_1w1d", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=AC2:4ip+Binding+Site+For+Chain+A'>AC2</scene>
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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=4IP:INOSITOL-(1,3,4,5)-TETRAKISPHOSPHATE'>4IP</scene>, <scene name='pdbligand=AU:GOLD+ION'>AU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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_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>
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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_1w1d| PDB=1w1d | 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=1w1d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w1d OCA], [http://www.ebi.ac.uk/pdbsum/1w1d PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1w1d RCSB]</span>
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}}
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'''CRYSTAL STRUCTURE OF THE PDK1 PLECKSTRIN HOMOLOGY (PH) DOMAIN BOUND TO INOSITOL (1,3,4,5)-TETRAKISPHOSPHATE'''
'''CRYSTAL STRUCTURE OF THE PDK1 PLECKSTRIN HOMOLOGY (PH) DOMAIN BOUND TO INOSITOL (1,3,4,5)-TETRAKISPHOSPHATE'''
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[[Category: Deak, M.]]
[[Category: Deak, M.]]
[[Category: Komander, D.]]
[[Category: Komander, D.]]
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[[Category: inositol phosphate]]
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[[Category: Inositol phosphate]]
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[[Category: pdk1]]
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[[Category: Pdk1]]
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[[Category: phosphoinositide]]
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[[Category: Phosphoinositide]]
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[[Category: phosphoinositide dependent protein kinase 1]]
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[[Category: Phosphoinositide dependent protein kinase 1]]
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[[Category: pi3-kinase]]
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[[Category: Pi3-kinase]]
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[[Category: pkb]]
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[[Category: Pkb]]
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[[Category: pleckstrin homology domain]]
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[[Category: Pleckstrin homology domain]]
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[[Category: serine/threonine protein kinase]]
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[[Category: Serine/threonine protein kinase]]
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[[Category: signal transduction]]
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[[Category: Signal transduction]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 13:01:13 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:29:44 2008''
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Revision as of 10:01, 3 May 2008

Image:1w1d.gif

Template:STRUCTURE 1w1d

CRYSTAL STRUCTURE OF THE PDK1 PLECKSTRIN HOMOLOGY (PH) DOMAIN BOUND TO INOSITOL (1,3,4,5)-TETRAKISPHOSPHATE


Overview

3-phosphoinositide-dependent protein kinase-1 (PDK1) phosphorylates and activates many kinases belonging to the AGC subfamily. PDK1 possesses a C-terminal pleckstrin homology (PH) domain that interacts with PtdIns(3,4,5)P3/PtdIns(3,4)P2 and with lower affinity to PtdIns(4,5)P2. We describe the crystal structure of the PDK1 PH domain, in the absence and presence of PtdIns(3,4,5)P3 and Ins(1,3,4,5)P4. The structures reveal a 'budded' PH domain fold, possessing an N-terminal extension forming an integral part of the overall fold, and display an unusually spacious ligand-binding site. Mutagenesis and lipid-binding studies were used to define the contribution of residues involved in phosphoinositide binding. Using a novel quantitative binding assay, we found that Ins(1,3,4,5,6)P5 and InsP6, which are present at micromolar levels in the cytosol, interact with full-length PDK1 with nanomolar affinities. Utilising the isolated PDK1 PH domain, which has reduced affinity for Ins(1,3,4,5,6)P5/InsP6, we perform localisation studies that suggest that these inositol phosphates serve to anchor a portion of cellular PDK1 in the cytosol, where it could activate its substrates such as p70 S6-kinase and p90 ribosomal S6 kinase that do not interact with phosphoinositides.

About this Structure

1W1D is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural insights into the regulation of PDK1 by phosphoinositides and inositol phosphates., Komander D, Fairservice A, Deak M, Kular GS, Prescott AR, Peter Downes C, Safrany ST, Alessi DR, van Aalten DM, EMBO J. 2004 Oct 13;23(20):3918-28. Epub 2004 Sep 30. PMID:15457207 Page seeded by OCA on Sat May 3 13:01:13 2008

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