1oky

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[[Image:1oky.jpg|left|200px]]
[[Image:1oky.jpg|left|200px]]
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{{Structure
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<!--
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|PDB= 1oky |SIZE=350|CAPTION= <scene name='initialview01'>1oky</scene>, resolution 2.30&Aring;
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The line below this paragraph, containing "STRUCTURE_1oky", creates the "Structure Box" on the page.
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|SITE= <scene name='pdbsite=AC9:Sto+Binding+Site+For+Chain+A'>AC9</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=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=STU:STAUROSPORINE'>STU</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_1oky| PDB=1oky | 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=1oky FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oky OCA], [http://www.ebi.ac.uk/pdbsum/1oky PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1oky RCSB]</span>
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}}
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'''STRUCTURE OF HUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH STAUROSPORINE'''
'''STRUCTURE OF HUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH STAUROSPORINE'''
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[[Category: Komander, D.]]
[[Category: Komander, D.]]
[[Category: Kular, G S.]]
[[Category: Kular, G S.]]
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[[Category: pdk1]]
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[[Category: Pdk1]]
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[[Category: pkb]]
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[[Category: Pkb]]
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[[Category: protein kinase]]
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[[Category: Protein kinase]]
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[[Category: staurosporine]]
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[[Category: Staurosporine]]
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[[Category: transferase]]
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[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 03:59:05 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:46:51 2008''
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Revision as of 00:59, 3 May 2008

Image:1oky.jpg

Template:STRUCTURE 1oky

STRUCTURE OF HUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH STAUROSPORINE


Overview

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.

About this Structure

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

Reference

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 Page seeded by OCA on Sat May 3 03:59:05 2008

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