Interaction of adenosine nucleotide analogs with Saccharomyces cerevisiae phosphoenolpyruvate carboxykinase

Loreto Carrasco, Fernando D. González, Emilio Cardemil

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5 Citations (Scopus)

Abstract

The substrate characteristics and interactions of different adenosine nucleotide analogs with Saccharomyces cerevisiae phosphoenolpyruvate (PEP) carboxykinase were investigated by steady-state kinetic analysis and calculations of interaction energies. Comparison of V(max)/K(m) values showed that analogs substituted at C8 in the adenine ring (8-Br-ATP, 8-N3-ATP, 8-N3-ADP) gave almost the same kinetic values as ATP and ADP, whereas those substituted in the ribose hydroxyls (3'(2')-O-(N-methylanthraniloyl)-ATP (MANT-ATP), 3'(2')-O-(N-methylanthraniloyl)-ADP (MANT-ADP), 2'(3')-O-(2,4,6-trinitrophenyl)-ADP (TNP-ADP), 2'(3')-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP)) showed 1-8% the value for the corresponding physiological substrate. A comparison between the experimental results and molecular mechanics calculations was performed, employing a model for the S. cerevisiae PEP carboxykinase-ATP-Mn2+ complex. The calculated interaction energies of S. cerevisiae PEP carboxykinase with ATP, MANT-ATP, TNP-ATP, 8-Br-ATP, and 8-N3-ATP were linearly related (correlation coefficient 0.92) with -ln(V(max)/K(m)). This good correlation supports the proposal that the interaction of the substituent with the enzyme affects the interaction of the common region of ATP with the active site, thus leading to effects in V(max). Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)93-101
Number of pages9
JournalBiochimica et Biophysica Acta - Protein Structure and Molecular Enzymology
Volume1429
Issue number1
DOIs
Publication statusPublished - 8 Dec 1998

Keywords

  • Homology modeling
  • Interaction energy
  • Nucleotide analog
  • Phosphoenolpyruvate carboxykinase
  • Saccharomyces cerevisiae

ASJC Scopus subject areas

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Molecular Biology

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