Structural and biochemical characterization of inhibitor-1alpha |
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Authors: | Huang Hsien-Bin Chen Yi-Chen Lee Ting-Ting Huang Yi-Choang Liu Hsin-Tzu Liu Chen-Kuang Tsay Huey-Jen Lin Ta-Hsien |
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Institution: | Institute of Molecular Biology, National Chung Cheng University, Chia-Yi 621, Taiwan, Republic of China. |
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Abstract: | Inhibitor-1alpha is one of the isoforms of human protein phosphatase inhibitor-1. It is a product of alternative splicing of inhibitor-1 gene and lacks 51 internal amino acids from residue 84 to 134 of inhibitor-1. Here we have characterized the structural and biochemical properties of inhibitor-1alpha. Structural analysis of recombinant inhibitor-1alpha by NMR spectroscopy revealed that inhibitor-1alpha adopts a predominantly random coil conformation. Excluding the region from residue 84 to 134 of inhibitor-1, the structural features of inhibitor-1 and inhibitor-1alpha are almost the same as each other. The IC(50) value of inhibitor-1alpha in inhibition of Protein phosphatase-1 (PP1) is comparable to that of inhibitor-1, indicating that inhibitor-1alpha is a potent inhibitor of PP1 when Thr-35 is phosphorylated by PKA. For phosphorylation by PKA and dephosphorylation by protein phosphatase-1, -2A, and -2B, the measured kinetic parameters of inhibitor-1alpha are very close to those of inhibitor-1. Taken together, these results suggest that inhibitor-1alpha preserves the structure of inhibitor-1, the PP1 inhibitory activity and the functional specificities toward phosphorylation by PKA and dephosphorylation by protein phosphatase-1, -2A, and -2B. |
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Keywords: | protein phosphatase‐1 inhibitor‐1 PKA NMR phosphorylation dephosphorylation |
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