1dc2: Difference between revisions
New page: left|200px<br /> <applet load="1dc2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dc2" /> '''SOLUTION NMR STRUCTURE OF TUMOR SUPPRESSOR ... |
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'''SOLUTION NMR STRUCTURE OF TUMOR SUPPRESSOR P16INK4A, 20 STRUCTURES'''<br /> | '''SOLUTION NMR STRUCTURE OF TUMOR SUPPRESSOR P16INK4A, 20 STRUCTURES'''<br /> | ||
==Overview== | ==Overview== | ||
Within the tumor suppressor protein INK4 (inhibitor of cyclin-dependent | Within the tumor suppressor protein INK4 (inhibitor of cyclin-dependent kinase 4) family, p15INK4B is the smallest and the only one whose structure has not been determined previously, probably due to the protein's conformational flexibility and instability. In this work, multidimensional NMR studies were performed on this protein. The first tertiary structure was built by comparative modeling with p16INK4A as the template, followed by restrained energy minimization with NMR constraints (NOE and H-bonds). For this purpose, the solution structure of pl6INK4A, whose quality was also limited by similar problems, was refined with additional NMR experiments conducted on an 800 MHz spectrometer and by structure-based iterative NOE assignments. The nonhelical regions showed major improvement with root-mean-square deviation (RMSD) improved from 1.23 to 0.68 A for backbone heavy atoms. The completion of p15INK4B coupled with refinement of p16INK4A made it possible to compare the structures of the four INK4 members in depth, and to compare the structures of p16INK4A in the free form and in the p16INK4A-CDK6 complex. This is an important step toward a comprehensive understanding of the precise functional roles of each INK4 member. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
1DC2 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:// | 1DC2 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=1DC2 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Byeon, I | [[Category: Byeon, I J.L.]] | ||
[[Category: Li, J.]] | [[Category: Li, J.]] | ||
[[Category: Tsai, M | [[Category: Tsai, M D.]] | ||
[[Category: Yuan, C.]] | [[Category: Yuan, C.]] | ||
[[Category: ankyrin repeat]] | [[Category: ankyrin repeat]] | ||
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[[Category: helix-turn-helix]] | [[Category: helix-turn-helix]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:15:04 2008'' | ||
Revision as of 13:15, 21 February 2008
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SOLUTION NMR STRUCTURE OF TUMOR SUPPRESSOR P16INK4A, 20 STRUCTURES
OverviewOverview
Within the tumor suppressor protein INK4 (inhibitor of cyclin-dependent kinase 4) family, p15INK4B is the smallest and the only one whose structure has not been determined previously, probably due to the protein's conformational flexibility and instability. In this work, multidimensional NMR studies were performed on this protein. The first tertiary structure was built by comparative modeling with p16INK4A as the template, followed by restrained energy minimization with NMR constraints (NOE and H-bonds). For this purpose, the solution structure of pl6INK4A, whose quality was also limited by similar problems, was refined with additional NMR experiments conducted on an 800 MHz spectrometer and by structure-based iterative NOE assignments. The nonhelical regions showed major improvement with root-mean-square deviation (RMSD) improved from 1.23 to 0.68 A for backbone heavy atoms. The completion of p15INK4B coupled with refinement of p16INK4A made it possible to compare the structures of the four INK4 members in depth, and to compare the structures of p16INK4A in the free form and in the p16INK4A-CDK6 complex. This is an important step toward a comprehensive understanding of the precise functional roles of each INK4 member.
DiseaseDisease
Known diseases associated with this structure: Li Fraumeni syndrome OMIM:[600160], Melanoma and neural system tumor syndrome OMIM:[600160], Melanoma, cutaneous malignant, 2 OMIM:[600160], Orolaryngeal cancer, multiple, OMIM:[600160], Pancreatic cancer/melanoma syndrome OMIM:[600160]
About this StructureAbout this Structure
1DC2 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Tumor suppressor INK4: refinement of p16INK4A structure and determination of p15INK4B structure by comparative modeling and NMR data., Yuan C, Selby TL, Li J, Byeon IJ, Tsai MD, Protein Sci. 2000 Jun;9(6):1120-8. PMID:10892805
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