1xjd
From Proteopedia
(New page: 200px<br /> <applet load="1xjd" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xjd, resolution 2.00Å" /> '''Crystal Structure o...) |
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| - | [[Image:1xjd.gif|left|200px]]<br /> | + | [[Image:1xjd.gif|left|200px]]<br /><applet load="1xjd" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1xjd" size=" | + | |
caption="1xjd, resolution 2.00Å" /> | caption="1xjd, resolution 2.00Å" /> | ||
'''Crystal Structure of PKC-theta complexed with Staurosporine at 2A resolution'''<br /> | '''Crystal Structure of PKC-theta complexed with Staurosporine at 2A resolution'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A member of the novel protein kinase C (PKC) subfamily, PKC, is an | + | A member of the novel protein kinase C (PKC) subfamily, PKC, is an essential component of the T cell synapse and is required for optimal T cell activation and interleukin-2 production. Selective involvement of PKC in TCR signaling makes this enzyme an attractive therapeutic target in T cell-mediated disease processes. In this report we describe the crystal structure of the catalytic domain of PKC at 2.0-A resolution. Human recombinant PKC kinase domain was expressed in bacteria as catalytically active phosphorylated enzyme and co-crystallized with its subnanomolar, ATP site inhibitor staurosporine. The structure follows the classic bilobal kinase fold and shows the enzyme in its active conformation and phosphorylated state. Inhibitory interactions between conserved features of staurosporine and the ATP-binding cleft are accompanied by closing of the glycine-rich loop, which also maintains an inhibitory arrangement by blocking the phosphate recognition subsite. The two major phosphorylation sites, Thr-538 in the activation loop and Ser-695 in the hydrophobic motif, are both occupied in the structure, playing key roles in stabilizing active conformation of the enzyme and indicative of PKC autocatalytic phosphorylation and activation during bacterial expression. The PKC-staurosporine complex represents the first kinase domain crystal structure of any PKC isotypes to be determined and as such should provide valuable insight into PKC specificity and into rational drug design strategies for PKC selective leads. |
==About this Structure== | ==About this Structure== | ||
| - | 1XJD 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 STU as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1XJD 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=STU:'>STU</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XJD OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Xu, Z | + | [[Category: Xu, Z B.]] |
[[Category: STU]] | [[Category: STU]] | ||
[[Category: amp]] | [[Category: amp]] | ||
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[[Category: pkc-theta]] | [[Category: pkc-theta]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:55:22 2008'' |
Revision as of 13:55, 21 February 2008
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Crystal Structure of PKC-theta complexed with Staurosporine at 2A resolution
Overview
A member of the novel protein kinase C (PKC) subfamily, PKC, is an essential component of the T cell synapse and is required for optimal T cell activation and interleukin-2 production. Selective involvement of PKC in TCR signaling makes this enzyme an attractive therapeutic target in T cell-mediated disease processes. In this report we describe the crystal structure of the catalytic domain of PKC at 2.0-A resolution. Human recombinant PKC kinase domain was expressed in bacteria as catalytically active phosphorylated enzyme and co-crystallized with its subnanomolar, ATP site inhibitor staurosporine. The structure follows the classic bilobal kinase fold and shows the enzyme in its active conformation and phosphorylated state. Inhibitory interactions between conserved features of staurosporine and the ATP-binding cleft are accompanied by closing of the glycine-rich loop, which also maintains an inhibitory arrangement by blocking the phosphate recognition subsite. The two major phosphorylation sites, Thr-538 in the activation loop and Ser-695 in the hydrophobic motif, are both occupied in the structure, playing key roles in stabilizing active conformation of the enzyme and indicative of PKC autocatalytic phosphorylation and activation during bacterial expression. The PKC-staurosporine complex represents the first kinase domain crystal structure of any PKC isotypes to be determined and as such should provide valuable insight into PKC specificity and into rational drug design strategies for PKC selective leads.
About this Structure
1XJD is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Catalytic domain crystal structure of protein kinase C-theta (PKCtheta)., Xu ZB, Chaudhary D, Olland S, Wolfrom S, Czerwinski R, Malakian K, Lin L, Stahl ML, Joseph-McCarthy D, Benander C, Fitz L, Greco R, Somers WS, Mosyak L, J Biol Chem. 2004 Nov 26;279(48):50401-9. Epub 2004 Sep 13. PMID:15364937
Page seeded by OCA on Thu Feb 21 15:55:22 2008
Categories: Homo sapiens | Single protein | Xu, Z B. | STU | Amp | Atp | Kinase | Pkc-theta
