1okz
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1okz |SIZE=350|CAPTION= <scene name='initialview01'>1okz</scene>, resolution 2.51Å | |PDB= 1okz |SIZE=350|CAPTION= <scene name='initialview01'>1okz</scene>, resolution 2.51Å | ||
|SITE= <scene name='pdbsite=BC3:Ucn+Binding+Site+For+Chain+A'>BC3</scene> | |SITE= <scene name='pdbsite=BC3:Ucn+Binding+Site+For+Chain+A'>BC3</scene> | ||
| - | |LIGAND= <scene name='pdbligand= | + | |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=UCN:7-HYDROXYSTAUROSPORINE'>UCN</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/ | + | |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> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<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.ebi.ac.uk/pdbsum/1okz PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1okz RCSB]</span> | ||
}} | }} | ||
| Line 21: | Line 24: | ||
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:[http://www.ncbi.nlm.nih.gov/pubmed/12892559 12892559] | 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:[http://www.ncbi.nlm.nih.gov/pubmed/12892559 12892559] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
| + | [[Category: Non-specific serine/threonine protein kinase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Transferred entry: 2 7.11 1]] | ||
[[Category: Aalten, D M.F Van.]] | [[Category: Aalten, D M.F Van.]] | ||
[[Category: Alessi, D R.]] | [[Category: Alessi, D R.]] | ||
[[Category: Komander, D.]] | [[Category: Komander, D.]] | ||
[[Category: Kular, G S.]] | [[Category: Kular, G S.]] | ||
| - | [[Category: GOL]] | ||
| - | [[Category: SO4]] | ||
| - | [[Category: UCN]] | ||
[[Category: 7-hydroxy staurosporine]] | [[Category: 7-hydroxy staurosporine]] | ||
[[Category: atp-binding]] | [[Category: atp-binding]] | ||
| Line 40: | Line 40: | ||
[[Category: ucn-01]] | [[Category: ucn-01]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:46:51 2008'' |
Revision as of 19:46, 30 March 2008
| |||||||
| , resolution 2.51Å | |||||||
|---|---|---|---|---|---|---|---|
| Sites: | |||||||
| Ligands: | , , , | ||||||
| Activity: | Non-specific serine/threonine protein kinase, with EC number 2.7.11.1 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURE OF HUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH UCN-01
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
1OKZ 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 Sun Mar 30 22:46:51 2008
