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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Haste, Nina M. Eyck, Lynn F. Ten Kornev, Alexandr P. Taylor, Susan S. |
| Description | Author Affiliation: Kornev AP ( San Diego Supercomputer Center, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.); |
| Abstract | The surface comparison of different serine-threonine and tyrosine kinases reveals a set of 30 residues whose spatial positions are highly conserved. The comparison between active and inactive conformations identified the residues whose positions are the most sensitive to activation. Based on these results, we propose a model of protein kinase activation. This model explains how the presence of a phosphate group in the activation loop determines the position of the catalytically important aspartate in the Asp-Phe-Gly motif. According to the model, the most important feature of the activation is a 'spine' formation that is dynamically assembled in all active kinases. The spine is comprised of four hydrophobic residues that we detected in a set of 23 eukaryotic and prokaryotic kinases. It spans the molecule and plays a coordinating role in activated kinases. The spine is disordered in the inactive kinases and can explain how stabilization of the whole molecule is achieved upon phosphorylation. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 47 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-11-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Algorithms Cyclic AMP-Dependent Protein Kinases Metabolism Cyclin-Dependent Kinase 2 Enzyme Activation Amino Acid Sequence Chemistry Genetics Hydrophobic And Hydrophilic Interactions Models, Molecular Phosphorylation Protein Structure, Tertiary Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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