Protein phosphatase 1 catalyses the direct hydrolytic cleavage of phosphate monoester in a ternary complex mechanism
| Autor: | Jonathan Sanvoisin, David Gani |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
chemistry.chemical_classification
Phosphoric monoester hydrolases Phosphopeptide Stereochemistry Hydrolysis Organic Chemistry Clinical Biochemistry Pharmaceutical Science Substrate (chemistry) Phosphate Biochemistry Catalysis Phosphates chemistry.chemical_compound Enzyme chemistry Protein Phosphatase 1 Drug Discovery Phosphoprotein Phosphatases Molecular Medicine Phosphorylation Binding site Molecular Biology Ternary complex |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 11:471-474 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/s0960-894x(00)00694-6 |
| Popis: | The catalytic subunit of the Ser/Thr protein phosphatase 1 (PP1 cat ) hydrolyses N -acetyl Arg-Arg-Ala-phosphoThr-Val-Ala ( K M =3.7 mM) in a reaction that is inhibited competitively by inorganic phosphate (P i , K i =1.6 mM) but unaffected by the product peptide alcohol at concentrations up to 3 mM. The enzyme does not catalyse the incorporation of 18 O-label from 18 O-labelled water into P i whether, or not, the product alcohol is present. The dephosphorylated product alcohol of phosphorylated histone, an alternative substrate for the enzyme, serves as a competitive inhibitor for phosphopeptide hydrolysis ( K i =60 μM) and co-mediates 18 O-label exchange into P i in a concentration-dependent manner ( K M =64 μM). These results indicate that hydrolysis occurs through the direct attack of an activated water molecule on the phosphate ester moiety of the substrate in a ternary complex mechanism. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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