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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Tang, Xiao-bo Turley, Stewart Hol, Wim G. J. Glavas, Natalie A. Martinez, Sergio E. Wu, Albert Y. Beavo, Joseph A. |
| Description | Author Affiliation: Martinez SE ( Departments of Pharmacology, and Biochemistry and Biological Structure, Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA.); |
| Abstract | Cyclic nucleotide phosphodiesterases (PDEs) regulate all pathways that use cGMP or cAMP as a second messenger. Five of the 11 PDE families have regulatory segments containing GAF domains, 3 of which are known to bind cGMP. In PDE2 binding of cGMP to the GAF domain causes an activation of the catalytic activity by a mechanism that apparently is shared even in the adenylyl cyclase of Anabaena, an organism separated from mouse by 2 billion years of evolution. The 2.9-A crystal structure of the mouse PDE2A regulatory segment reported in this paper reveals that the GAF A domain functions as a dimerization locus. The GAF B domain shows a deeply buried cGMP displaying a new cGMP-binding motif and is the first atomic structure of a physiological cGMP receptor with bound cGMP. Moreover, this cGMP site is located well away from the region predicted by previous mutagenesis and structural genomic approaches. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 20 |
| Volume Number | 99 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2002-10-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | 3',5'-Cyclic-AMP Phosphodiesterases Chemistry Metabolism Amino Acid Motifs Amino Acid Sequence Animals Crystallography, X-Ray Cyclic AMP Cyclic GMP Cyclic Nucleotide Phosphodiesterases, Type 2 Dimerization Dose-Response Relationship, Drug Mice Models, Biological Models, Molecular Molecular Sequence Data Protein Binding Protein Conformation Protein Structure, Quaternary Protein Structure, Tertiary Sequence Homology, Amino Acid Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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