1w1h: Difference between revisions

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Revision as of 15:50, 20 March 2008

File:1w1h.gif

, resolution 1.45Å

Sites:

Ligands:

and

Activity:

Transferred entry: 2.7.11.1, with EC number 2.7.1.37

Coordinates:

save as pdb, mmCIF, xml

CRYSTAL STRUCTURE OF THE PDK1 PLECKSTRIN HOMOLOGY (PH) DOMAIN

OverviewOverview

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 StructureAbout this Structure

1W1H is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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

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OCA

@@ Line 1: / Line 1: @@
-[[Image:1w1h.gif|left|200px]]<br /><applet load="1w1h" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:1w1h.gif|left|200px]]
-caption="1w1h, resolution 1.45&Aring;" />
-'''CRYSTAL STRUCTURE OF THE PDK1 PLECKSTRIN HOMOLOGY (PH) DOMAIN'''<br />
+ {{Structure
+|PDB= 1w1h |SIZE=350|CAPTION= <scene name='initialview01'>1w1h</scene>, resolution 1.45&Aring;
+|SITE= <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+B'>AC1</scene>
+|LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>
+|ACTIVITY= [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.1 Transferred entry: 2.7.11.1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.37 2.7.1.37]
+|GENE=
+}}
+'''CRYSTAL STRUCTURE OF THE PDK1 PLECKSTRIN HOMOLOGY (PH) DOMAIN'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-W1H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO4:'>SO4</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Transferred_entry:_2.7.11.1 Transferred entry: 2.7.11.1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.37 2.7.1.37] Known structural/functional Site: <scene name='pdbsite=AC1:So4+Binding+Site+For+Chain+B'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W1H OCA].
+W1H is a [[Single protein]] structure of 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=1W1H 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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=15457207 15457207]
+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:[http://www.ncbi.nlm.nih.gov/pubmed/15457207 15457207]
 [[Category: Homo sapiens]]
 [[Category: Single protein]]
@@ Line 30: / Line 39: @@
 [[Category: transferase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:39:27 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:50:45 2008''