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Structural and biochemical characterization of inhibitor‐1α
Author(s) -
Huang HsienBin,
Chen YiChen,
Lee TingTing,
Huang YiChoang,
Liu HsinTzu,
Liu ChenKuang,
Tsay HueyJen,
Lin TaHsien
Publication year - 2007
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.21438
Subject(s) - dephosphorylation , inhibitor protein , protein phosphatase 1 , protein kinase inhibitor , enzyme inhibitor , phosphatase , phosphorylation , biochemistry , dusp6 , chemistry , residue (chemistry) , protease inhibitor (pharmacology) , biology , enzyme , protein phosphatase 2 , protein kinase a , human immunodeficiency virus (hiv) , antiretroviral therapy , viral load , immunology
Inhibitor‐1α 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‐1α. Structural analysis of recombinant inhibitor‐1α by NMR spectroscopy revealed that inhibitor‐1α 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‐1α are almost the same as each other. The IC 50 value of inhibitor‐1α in inhibition of Protein phosphatase‐1 (PP1) is comparable to that of inhibitor‐1, indicating that inhibitor‐1α 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‐1α are very close to those of inhibitor‐1. Taken together, these results suggest that inhibitor‐1α 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. Proteins 2007. © 2007 Wiley‐Liss, Inc.