1oky

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:1oky.jpg|left|200px]]
+
{{Seed}}
 +
[[Image:1oky.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_1oky| PDB=1oky | SCENE= }}
{{STRUCTURE_1oky| PDB=1oky | SCENE= }}
-
'''STRUCTURE OF HUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH STAUROSPORINE'''
+
===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.
+
The line below this paragraph, {{ABSTRACT_PUBMED_12892559}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 12892559 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_12892559}}
==About this Structure==
==About this Structure==
Line 32: Line 36:
[[Category: Staurosporine]]
[[Category: Staurosporine]]
[[Category: Transferase]]
[[Category: Transferase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 03:59:05 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 15:08:33 2008''

Revision as of 12:08, 28 July 2008

Image:1oky.png

Template:STRUCTURE 1oky

STRUCTURE OF HUMAN PDK1 KINASE DOMAIN IN COMPLEX WITH STAUROSPORINE

Template:ABSTRACT PUBMED 12892559

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 Mon Jul 28 15:08:33 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1oky"
Personal tools