1h1w

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{{STRUCTURE_1h1w| PDB=1h1w | SCENE= }}
{{STRUCTURE_1h1w| PDB=1h1w | SCENE= }}
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'''HIGH RESOLUTION CRYSTAL STRUCTURE OF THE HUMAN PDK1 CATALYTIC DOMAIN'''
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===HIGH RESOLUTION CRYSTAL STRUCTURE OF THE HUMAN PDK1 CATALYTIC DOMAIN===
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==Overview==
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3-phosphoinositide dependent protein kinase-1 (PDK1) plays a key role in regulating signalling pathways by activating AGC kinases such as PKB/Akt and S6K. Here we describe the 2.0 A crystal structure of the PDK1 kinase domain in complex with ATP. The structure defines the hydrophobic pocket termed the "PIF-pocket", which plays a key role in mediating the interaction and phosphorylation of certain substrates such as S6K1. Phosphorylation of S6K1 at its C-terminal PIF-pocket-interacting motif promotes the binding of S6K1 with PDK1. In the PDK1 structure, this pocket is occupied by a crystallographic contact with another molecule of PDK1. Interestingly, close to the PIF-pocket in PDK1, there is an ordered sulfate ion, interacting tightly with four surrounding side chains. The roles of these residues were investigated through a combination of site-directed mutagenesis and kinetic studies, the results of which confirm that this region of PDK1 represents a phosphate-dependent docking site. We discuss the possibility that an analogous phosphate-binding regulatory motif may participate in the activation of other AGC kinases. Furthermore, the structure of PDK1 provides a scaffold for the design of specific PDK1 inhibitors.
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(as it appears on PubMed at http://www.pubmed.gov), where 12169624 is the PubMed ID number.
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{{ABSTRACT_PUBMED_12169624}}
==About this Structure==
==About this Structure==
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[[Category: Serine/threonine-protein kinase]]
[[Category: Serine/threonine-protein kinase]]
[[Category: Transferase]]
[[Category: Transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 1 06:28:56 2008''

Revision as of 03:29, 1 July 2008

Image:1h1w.png

Template:STRUCTURE 1h1w

HIGH RESOLUTION CRYSTAL STRUCTURE OF THE HUMAN PDK1 CATALYTIC DOMAIN

Template:ABSTRACT PUBMED 12169624

About this Structure

1H1W is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

High resolution crystal structure of the human PDK1 catalytic domain defines the regulatory phosphopeptide docking site., Biondi RM, Komander D, Thomas CC, Lizcano JM, Deak M, Alessi DR, van Aalten DM, EMBO J. 2002 Aug 15;21(16):4219-28. PMID:12169624

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