Structural Basis for the Catalytic Activity of Human Serine/Threonine Protein Phosphatase-5
| Autor: | Richard E. Honkanen, Mark R. Swingle, Ewa Ciszak |
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| Rok vydání: | 2004 |
| Předmět: |
Models
Molecular Chemical Phenomena Stereochemistry Recombinant Fusion Proteins Static Electricity Phosphatase Gene Expression Crystallography X-Ray Biochemistry Catalysis Serine Structure-Activity Relationship Phosphoprotein Phosphatases Humans Molecule Amino Acid Sequence Threonine Molecular Biology Conserved Sequence Binding Sites Molecular Structure Chemistry Physical Chemistry Cell growth Hydrolysis C-terminus Nuclear Proteins Cell Biology Peptide Fragments Phosphoprotein Crystallization Sequence Alignment |
| Zdroj: | Journal of Biological Chemistry. 279:33992-33999 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m402855200 |
| Popis: | Serine/threonine protein phosphatase-5 (PP5) affects many signaling networks that regulate cell growth and cellular responses to stress. Here we report the crystal structure of the PP5 catalytic domain (PP5c) at a resolution of 1.6 A. From this structure we propose a mechanism for PP5-mediated hydrolysis of phosphoprotein substrates, which requires the precise positioning of two metal ions within a conserved Asp271-M1:M2-W1-His427-His304-Asp274 catalytic motif (where M1 and M2 are metals and W1 is a water molecule). The structure of PP5c provides a structural basis for explaining the exceptional catalytic proficiency of protein phosphatases, which are among the most powerful known catalysts. Resolution of the entire C terminus revealed a novel subdomain, and the structure of the PP5c should also aid development of type-specific inhibitors. |
| Databáze: | OpenAIRE |
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