2vge
From Proteopedia
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caption="2vge, resolution 2.10Å" /> | caption="2vge, resolution 2.10Å" /> | ||
'''CRYSTAL STRUCTURE OF THE C-TERMINAL REGION OF HUMAN IASPP'''<br /> | '''CRYSTAL STRUCTURE OF THE C-TERMINAL REGION OF HUMAN IASPP'''<br /> | ||
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| + | ==Overview== | ||
| + | ASPP1 and ASPP2 are activators of p53-dependent apoptosis, whereas iASPP is an inhibitor of p53. Binding assays showed differential binding for C-terminal domains of iASPP and ASPP2 to the core domains of p53 family members p53, p63, and p73. We also determined a high-resolution crystal structure for the C terminus of iASPP, comprised of four ankyrin repeats and an SH3 domain. The crystal lattice revealed an interaction between eight sequential residues in one iASPP molecule and the p53-binding site of a neighboring molecule. ITC confirmed that a peptide corresponding to the crystallographic interaction shows specific binding to iASPP. The contributions of ankyrin repeat residues, in addition to those of the SH3 domain, generate distinctive architecture at the p53-binding site suitable for inhibition by small molecules. These results suggest that the binding properties of iASPP render it a target for antitumor therapeutics and provide a peptide-based template for compound design. | ||
==About this Structure== | ==About this Structure== | ||
2VGE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VGE OCA]. | 2VGE is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VGE OCA]. | ||
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| + | ==Reference== | ||
| + | Biochemical and Structural Studies of ASPP Proteins Reveal Differential Binding to p53, p63, and p73., Robinson RA, Lu X, Jones EY, Siebold C, Structure. 2008 Feb;16(2):259-68. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18275817 18275817] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: transcription regulation]] | [[Category: transcription regulation]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 27 07:48:20 2008'' |
Revision as of 05:48, 27 February 2008
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CRYSTAL STRUCTURE OF THE C-TERMINAL REGION OF HUMAN IASPP
Overview
ASPP1 and ASPP2 are activators of p53-dependent apoptosis, whereas iASPP is an inhibitor of p53. Binding assays showed differential binding for C-terminal domains of iASPP and ASPP2 to the core domains of p53 family members p53, p63, and p73. We also determined a high-resolution crystal structure for the C terminus of iASPP, comprised of four ankyrin repeats and an SH3 domain. The crystal lattice revealed an interaction between eight sequential residues in one iASPP molecule and the p53-binding site of a neighboring molecule. ITC confirmed that a peptide corresponding to the crystallographic interaction shows specific binding to iASPP. The contributions of ankyrin repeat residues, in addition to those of the SH3 domain, generate distinctive architecture at the p53-binding site suitable for inhibition by small molecules. These results suggest that the binding properties of iASPP render it a target for antitumor therapeutics and provide a peptide-based template for compound design.
About this Structure
2VGE is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Biochemical and Structural Studies of ASPP Proteins Reveal Differential Binding to p53, p63, and p73., Robinson RA, Lu X, Jones EY, Siebold C, Structure. 2008 Feb;16(2):259-68. PMID:18275817
Page seeded by OCA on Wed Feb 27 07:48:20 2008
