1zrz
From Proteopedia
(New page: 200px<br /> <applet load="1zrz" size="450" color="white" frame="true" align="right" spinBox="true" caption="1zrz, resolution 3.00Å" /> '''Crystal Structure o...) |
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| - | [[Image:1zrz.gif|left|200px]]<br /> | + | [[Image:1zrz.gif|left|200px]]<br /><applet load="1zrz" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1zrz" size=" | + | |
caption="1zrz, resolution 3.00Å" /> | caption="1zrz, resolution 3.00Å" /> | ||
'''Crystal Structure of the Catalytic Domain of Atypical Protein Kinase C-iota'''<br /> | '''Crystal Structure of the Catalytic Domain of Atypical Protein Kinase C-iota'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Atypical protein kinases C (aPKCs) play critical roles in signaling | + | Atypical protein kinases C (aPKCs) play critical roles in signaling pathways that control cell growth, differentiation and survival. Therefore, they constitute attractive targets for the development of novel therapeutics against cancer. The crystal structure of the catalytic domain of atypical PKCiota in complex with the bis(indolyl)maleimide inhibitor BIM1 has been determined at 3.0A resolution within the frame of the European Structural Proteomics Project SPINE. The overall structure exhibits the classical bilobal kinase fold and is in its fully activated form. Both phosphorylation sites (Thr403 in the activation loop, and Thr555 in the turn motif) are well defined in the structure and form intramolecular ionic contacts that make an important contribution in stabilizing the active conformation of the catalytic subunit. The phosphorylation site in the hydrophobic motif of atypical PKCs is replaced by the phosphorylation mimic glutamate and this is also clearly seen in the structure of PKCiota (residue 574). This structure determination for the first time provides the architecture of the turn motif phosphorylation site, which is characteristic for PKCs and PKB/AKT, and is completely different from that in PKA. The bound BIM1 inhibitor blocks the ATP-binding site and puts the kinase domain into an intermediate open conformation. The PKCiota-BIM1 complex is the first kinase domain crystal structure of any atypical PKC and constitutes the basis for rational drug design for selective PKCiota inhibitors. |
==About this Structure== | ==About this Structure== | ||
| - | 1ZRZ 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 BI1 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1ZRZ 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=BI1:'>BI1</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1ZRZ OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Messerschmidt, A.]] | [[Category: Messerschmidt, A.]] | ||
[[Category: Neuefeind, T.]] | [[Category: Neuefeind, T.]] | ||
| - | [[Category: SPINE, Structural | + | [[Category: SPINE, Structural Proteomics in Europe.]] |
[[Category: Velarde, M.]] | [[Category: Velarde, M.]] | ||
[[Category: BI1]] | [[Category: BI1]] | ||
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[[Category: structural proteomics in europe]] | [[Category: structural proteomics in europe]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:18:35 2008'' |
Revision as of 14:18, 21 February 2008
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Crystal Structure of the Catalytic Domain of Atypical Protein Kinase C-iota
Overview
Atypical protein kinases C (aPKCs) play critical roles in signaling pathways that control cell growth, differentiation and survival. Therefore, they constitute attractive targets for the development of novel therapeutics against cancer. The crystal structure of the catalytic domain of atypical PKCiota in complex with the bis(indolyl)maleimide inhibitor BIM1 has been determined at 3.0A resolution within the frame of the European Structural Proteomics Project SPINE. The overall structure exhibits the classical bilobal kinase fold and is in its fully activated form. Both phosphorylation sites (Thr403 in the activation loop, and Thr555 in the turn motif) are well defined in the structure and form intramolecular ionic contacts that make an important contribution in stabilizing the active conformation of the catalytic subunit. The phosphorylation site in the hydrophobic motif of atypical PKCs is replaced by the phosphorylation mimic glutamate and this is also clearly seen in the structure of PKCiota (residue 574). This structure determination for the first time provides the architecture of the turn motif phosphorylation site, which is characteristic for PKCs and PKB/AKT, and is completely different from that in PKA. The bound BIM1 inhibitor blocks the ATP-binding site and puts the kinase domain into an intermediate open conformation. The PKCiota-BIM1 complex is the first kinase domain crystal structure of any atypical PKC and constitutes the basis for rational drug design for selective PKCiota inhibitors.
About this Structure
1ZRZ is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Crystal structure of the catalytic domain of human atypical protein kinase C-iota reveals interaction mode of phosphorylation site in turn motif., Messerschmidt A, Macieira S, Velarde M, Badeker M, Benda C, Jestel A, Brandstetter H, Neuefeind T, Blaesse M, J Mol Biol. 2005 Sep 30;352(4):918-31. PMID:16125198
Page seeded by OCA on Thu Feb 21 16:18:35 2008
Categories: Homo sapiens | Single protein | Baedeker, M. | Benda, C. | Blaesse, M. | Brandstetter, H. | Jestel, A. | Macieira, S. | Messerschmidt, A. | Neuefeind, T. | SPINE, Structural Proteomics in Europe. | Velarde, M. | BI1 | Protein-inhibitor complex | Spine | Structural genomics | Structural proteomics in europe
