1unp
From Proteopedia
(New page: 200px<br /> <applet load="1unp" size="450" color="white" frame="true" align="right" spinBox="true" caption="1unp, resolution 1.65Å" /> '''CRYSTAL STRUCTURE O...) |
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caption="1unp, resolution 1.65Å" /> | caption="1unp, resolution 1.65Å" /> | ||
'''CRYSTAL STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN OF PKB ALPHA'''<br /> | '''CRYSTAL STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN OF PKB ALPHA'''<br /> | ||
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==Disease== | ==Disease== | ||
| - | Known diseases associated with this structure: Neutrophil immunodeficiency syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602049 602049]], Schizophrenia, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164730 164730]] | + | Known diseases associated with this structure: Breast cancer, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164730 164730]], Colorectal cancer, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164730 164730]], Neutrophil immunodeficiency syndrome OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602049 602049]], Ovarian cancer, somatic OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164730 164730]], Schizophrenia, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=164730 164730]] |
==About this Structure== | ==About this Structure== | ||
| - | 1UNP 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:// | + | 1UNP 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=1UNP OCA]. |
==Reference== | ==Reference== | ||
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[[Category: transferase]] | [[Category: transferase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:03:33 2008'' |
Revision as of 15:03, 15 February 2008
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CRYSTAL STRUCTURE OF THE PLECKSTRIN HOMOLOGY DOMAIN OF PKB ALPHA
Contents |
Overview
Protein kinase B (PKB/Akt) is a key regulator of cell growth, proliferation and metabolism. It possesses an N-terminal pleckstrin, homology (PH) domain that interacts with equal affinity with the second, messengers PtdIns(3,4,5)P3 and PtdIns(3,4)P2, generated through insulin, and growth factor-mediated activation of phosphoinositide 3-kinase (PI3K)., The binding of PKB to PtdIns(3,4,5)P3/PtdIns(3,4)P2 recruits PKB from the, cytosol to the plasma membrane and is also thought to induce a, conformational change that converts PKB into a substrate that can be, activated by the phosphoinositide-dependent kinase 1 (PDK1). In this study, we describe two high-resolution crystal structures of the PH domain of, PKBalpha in a noncomplexed form and compare this to a new atomic, resolution (0.98 A, where 1 A=0.1 nm) structure of the PH domain of, PKBalpha complexed to Ins(1,3,4,5)P4, the head group of PtdIns(3,4,5)P3., Remarkably, in contrast to all other PH domains crystallized so far, our, data suggest that binding of Ins(1,3,4,5)P4 to the PH domain of PKB, induces a large conformational change. This is characterized by marked, changes in certain residues making up the phosphoinositide-binding site, formation of a short a-helix in variable loop 2, and a movement of, variable loop 3 away from the lipid-binding site. Solution studies with CD, also provided evidence of conformational changes taking place upon binding, of Ins(1,3,4,5)P4 to the PH domain of PKB. Our data provides the first, structural insight into the mechanism by which the interaction of PKB with, PtdIns(3,4,5)P3/PtdIns(3,4)P2 induces conformational changes that could, enable PKB to be activated by PDK1.
Disease
Known diseases associated with this structure: Breast cancer, somatic OMIM:[164730], Colorectal cancer, somatic OMIM:[164730], Neutrophil immunodeficiency syndrome OMIM:[602049], Ovarian cancer, somatic OMIM:[164730], Schizophrenia, susceptibility to OMIM:[164730]
About this Structure
1UNP is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Binding of phosphatidylinositol 3,4,5-trisphosphate to the pleckstrin homology domain of protein kinase B induces a conformational change., Milburn CC, Deak M, Kelly SM, Price NC, Alessi DR, Van Aalten DM, Biochem J. 2003 Nov 1;375(Pt 3):531-8. PMID:12964941
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