Structural Basis for the Substrate Specificity of Bone Morphogenetic Protein 1/Tolloid-like Metalloproteases
| Autor: | A. Hein, P. Erbel, S. Gil-Parrado, A. Bernardi, Ursula Bodendorf, D. Vinzenz, Bernd Gerhartz, C. Logel, A. Mac Sweeney |
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| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Proteases Magnetic Resonance Spectroscopy Tolloid-Like Metalloproteinases medicine.medical_treatment Molecular Sequence Data Astacoidea Crystallography X-Ray Bone morphogenetic protein Protein Structure Secondary Bone morphogenetic protein 1 Bone Morphogenetic Protein 1 Substrate Specificity Structural Biology medicine Animals Humans Amino Acid Sequence Enzyme Inhibitors Binding site Molecular Biology Metalloproteinase Binding Sites Protease biology Chemistry Metalloendopeptidases Active site Protein Structure Tertiary Kinetics Biochemistry Bone Morphogenetic Proteins Metalloproteases biology.protein Astacin Sequence Alignment |
| Zdroj: | Journal of Molecular Biology. 384:228-239 |
| ISSN: | 0022-2836 |
| Popis: | Procollagen C-peptidase, also known as bone morphogenetic protein 1 (BMP-1), is a multidomain, zinc endopeptidase of the astacin M12A family. BMP-1 is the prototype of a small group of proteases that have key roles in extracellular matrix formation and morphogenesis. BMP-1, its splice form mTLD, and the related proteases TLL-1 and TLL-2 are considered as promising drug targets for the treatment of excessive fibrosis and muscle wasting. We report here the crystal structures of the protease domains of human BMP-1 and the closely related Tolloid-like protease 1 (TLL-1). The crystal structures reveal an unexpected conformation of a cysteine-rich loop within the active site, and suggest that a flap movement is required in order to allow substrate binding. On the basis of these substantial differences between the BMP-1 and astacin active sites, a structural basis for their differing substrate specificities is proposed. |
| Databáze: | OpenAIRE |
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