Site-directed mutagenesis of rat muscle 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase: role of Asp-130 in the 2-kinase domain

Biochem J. 1994 May 15;300 ( Pt 1)(Pt 1):111-5. doi: 10.1042/bj3000111.

Abstract

Asp-130 of the recombinant skeletal-muscle 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase was mutated into Ala in order to study its role in catalysis and/or substrate binding. The D130A mutant displayed a 30- to 140-fold decreased 2-kinase Vmax, depending on the pH, and a 30- and 60-fold increase in Km for MgATP and Fru-6-P respectively at pH 8.5 compared with the wild-type. Mutagenesis of Asp-130 to Ala had no effect on the 2-phosphatase activity, and fluorescence measurements indicated that the changes in kinetic properties of PFK-2 in the D130A mutant were not due to instability. The role of Asp-130 in the 2-kinase reaction is discussed and compared with that of Asp-103 of 6-phosphofructo-1-kinase from Escherichia coli, which binds Mg2+.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aspartic Acid / genetics
  • Aspartic Acid / metabolism*
  • Base Sequence
  • Blotting, Western
  • Chromatography, Liquid
  • Electrophoresis, Polyacrylamide Gel
  • Fluorescence Polarization
  • Kinetics
  • Molecular Sequence Data
  • Muscles / enzymology*
  • Mutagenesis, Site-Directed
  • Oligodeoxyribonucleotides
  • Phosphofructokinase-2
  • Phosphoric Monoester Hydrolases / genetics
  • Phosphoric Monoester Hydrolases / isolation & purification
  • Phosphoric Monoester Hydrolases / metabolism*
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / isolation & purification
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Protein Conformation
  • Rats
  • Sequence Alignment

Substances

  • Oligodeoxyribonucleotides
  • Aspartic Acid
  • Phosphotransferases (Alcohol Group Acceptor)
  • Phosphofructokinase-2
  • Phosphoric Monoester Hydrolases