Purification from a yeast mutant of mitochondrial F1 with modified beta-subunit. High affinity for nucleotides and high negative cooperativity of ATPase activity

Biochim Biophys Acta. 1989 Jun 23;975(1):119-26. doi: 10.1016/s0005-2728(89)80209-9.

Abstract

Mitochondrial F1 containing genetically modified beta-subunit was purified for the first time from a mutant of the yeast Schizosaccharomyces pombe. Precipitation by poly(ethylene glycol) allowed us to obtain a very stable and pure enzyme from either mutant or wild-type strain. In the presence of EDTA, purified F1 retained high amounts of endogenous nucleotides: 4.6 mol/mol and 3.7 mol/mol for mutant and wild-type F1, respectively. The additional nucleotide in mutant F1 was ATP; it was lost in the presence of Mg2+, which led to a total of 3.4 mol of nucleotides/mol whereas wild-type F1 retained all its nucleotides. Mutant F1 bound more exogenous ADP than wild-type F1 and the same total nucleotide amount was reached with both enzymes. Kinetics of ATPase activity revealed a much higher negative cooperativity for mutant than for wild-type F1. Bicarbonate abolished this negative cooperativity, but higher concentrations were required for mutant F1. The mutant enzyme was more sensitive than the wild-type one to azide inhibition and ADP competitive inhibition; this indicated stronger interactions between nucleotide and F1 in the mutant enzyme. The latter also showed increased sensitivity to N,N'-dicyclohexylcarbodiimide irreversible inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / metabolism*
  • Adenosine Triphosphate / metabolism*
  • Chromatography, Gel
  • Kinetics
  • Macromolecular Substances
  • Magnesium / pharmacology
  • Mutation*
  • Protein Binding
  • Proton-Translocating ATPases / genetics
  • Proton-Translocating ATPases / isolation & purification
  • Proton-Translocating ATPases / metabolism*
  • Saccharomycetales / enzymology*
  • Schizosaccharomyces / enzymology*
  • Schizosaccharomyces / genetics
  • Submitochondrial Particles / enzymology*

Substances

  • Macromolecular Substances
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Proton-Translocating ATPases
  • Magnesium