Structural and biochemical characterization of inhibitor-1alpha

Proteins. 2007 Aug 15;68(3):779-88. doi: 10.1002/prot.21438.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Catalytic Domain
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • DNA, Complementary
  • Intracellular Signaling Peptides and Proteins / chemistry*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Kinetics
  • Nuclear Magnetic Resonance, Biomolecular
  • Nuclear Proteins
  • Phosphoprotein Phosphatases / antagonists & inhibitors*
  • Phosphorylation
  • Protein Conformation
  • Protein Phosphatase 1
  • RNA-Binding Proteins
  • Rabbits
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism

Substances

  • ANP32A protein, human
  • DNA, Complementary
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • RNA-Binding Proteins
  • Recombinant Proteins
  • Cyclic AMP-Dependent Protein Kinases
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 1