Glutamine 170 to tyrosine substitution in yeast mitochondrial F1 beta-subunit increases catalytic site interaction with GDP and IDP and produces negative cooperativity of GTP and ITP hydrolysis

J Biol Chem. 1993 Oct 5;268(28):20762-7.

Abstract

Glutamine 170 to tyrosine mutation in the beta-subunit from Schizosaccharomyces pombe mitochondrial F1 was found to increase both affinity for ADP, apparent negative cooperativity of ATPase activity, and sensitivity to azide inhibition (Falson, P., Di Pietro, A., Jault, J.-M., Gautheron, D.C., and Boutry, M. (1989) Biochim. Biophys. Acta 975, 119-126). The mutation is shown here to increase the affinity for GDP, IDP, and guanosine 5'-(beta,gamma-imidotriphosphate), which are competitive inhibitors of GTPase and ITPase activities. Various fluorescence approaches also reveal an increased affinity of the catalytic site in mutant as compared with wild-type enzyme for GDP, IDP, and 2'(3')-N-methylanthraniloyl GDP. The mutation alters the maximal rates and pH dependence of GTPase and ITPase activities, whereas wild-type F1 exhibits single optima at pH 7.5-8.0. The pH activity profiles of the mutant enzyme for these substrates are biphasic, with optima at pH 8.5-9.0 and below 6.5. The mutation increases the sensitivity of GTPase and ITPase activities to azide inhibition, which increases with decreasing pH. At pH 6.0-7.0, an apparent negative cooperativity is observed when mutant F1 hydrolyzes GTP or ITP, whereas the wild-type enzyme shows Michaelian kinetics. Addition of bicarbonate at pH 7.0 substantially stimulates GTP or ITP hydrolysis and abolishes the apparent negative cooperativity by the mutant enzyme; on the contrary, the anion produces a slight inhibition of these activities catalyzed by wild-type F1. The overall results suggest that apparent negative cooperativity can be observed with GTP or ITP hydrolysis provided that the release of the respective diphosphate is a rate-limiting step.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Azides / pharmacology
  • Bicarbonates / pharmacology
  • Catalysis
  • Enzyme Activation
  • GTP Phosphohydrolases / antagonists & inhibitors
  • Glutamine / metabolism*
  • Guanine Nucleotides / metabolism*
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / metabolism
  • Hydrogen-Ion Concentration
  • Hydrolysis
  • Inosine Diphosphate / metabolism
  • Inosine Nucleotides / metabolism*
  • Inosine Triphosphatase
  • Inosine Triphosphate / metabolism
  • Mitochondria / enzymology*
  • Proton-Translocating ATPases / chemistry
  • Proton-Translocating ATPases / metabolism*
  • Pyrophosphatases / antagonists & inhibitors
  • Schizosaccharomyces / enzymology*
  • Tyrosine / metabolism*

Substances

  • Azides
  • Bicarbonates
  • Guanine Nucleotides
  • Inosine Nucleotides
  • Glutamine
  • Inosine Triphosphate
  • Guanosine Diphosphate
  • Tyrosine
  • Guanosine Triphosphate
  • Inosine Diphosphate
  • GTP Phosphohydrolases
  • Pyrophosphatases
  • Proton-Translocating ATPases