Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva
Background: Mutations in the ALK2 kinase cause extraskeletal bone formation. Results: We solved the structure of ALK2 in complex with the inhibitor FKBP12. Conclusion: Disease mutations break critical interactions that stabilize the inactive ALK2-FKBP12 complex leading to kinase activation. Signific...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal article |
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2012
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| _version_ | 1797103727101870080 |
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| author | Chaikuad, A Alfano, I Kerr, G Sanvitale, C Boergermann, J Triffitt, J Von Delft, F Knapp, S Knaus, P Bullock, A |
| author_facet | Chaikuad, A Alfano, I Kerr, G Sanvitale, C Boergermann, J Triffitt, J Von Delft, F Knapp, S Knaus, P Bullock, A |
| author_sort | Chaikuad, A |
| collection | OXFORD |
| description | Background: Mutations in the ALK2 kinase cause extraskeletal bone formation. Results: We solved the structure of ALK2 in complex with the inhibitor FKBP12. Conclusion: Disease mutations break critical interactions that stabilize the inactive ALK2-FKBP12 complex leading to kinase activation. Significance: We offer an explanation for the effects of mutation and a structural template for the design of small molecule inhibitors. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. |
| first_indexed | 2024-03-07T06:24:14Z |
| format | Journal article |
| id | oxford-uuid:f3baf9ad-c9dd-4e8a-abcc-df9bce12be05 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T06:24:14Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:f3baf9ad-c9dd-4e8a-abcc-df9bce12be052022-03-27T12:14:16ZStructure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressivaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f3baf9ad-c9dd-4e8a-abcc-df9bce12be05Symplectic Elements at Oxford2012Chaikuad, AAlfano, IKerr, GSanvitale, CBoergermann, JTriffitt, JVon Delft, FKnapp, SKnaus, PBullock, ABackground: Mutations in the ALK2 kinase cause extraskeletal bone formation. Results: We solved the structure of ALK2 in complex with the inhibitor FKBP12. Conclusion: Disease mutations break critical interactions that stabilize the inactive ALK2-FKBP12 complex leading to kinase activation. Significance: We offer an explanation for the effects of mutation and a structural template for the design of small molecule inhibitors. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. |
| spellingShingle | Chaikuad, A Alfano, I Kerr, G Sanvitale, C Boergermann, J Triffitt, J Von Delft, F Knapp, S Knaus, P Bullock, A Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva |
| title | Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva |
| title_full | Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva |
| title_fullStr | Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva |
| title_full_unstemmed | Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva |
| title_short | Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva |
| title_sort | structure of the bone morphogenetic protein receptor alk2 and implications for fibrodysplasia ossificans progressiva |
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