Interaction of adenosine nucleotide analogs with Saccharomyces cerevisiae phosphoenolpyruvate carboxykinase

Loreto Carrasco, Fernando D. González, Emilio Cardemil

Resultado de la investigación: Article

5 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Páginas (desde-hasta)93-101
Número de páginas9
PublicaciónBiochimica et Biophysica Acta - Protein Structure and Molecular Enzymology
Volumen1429
N.º1
DOI
EstadoPublished - 8 dic 1998

Huella dactilar

Phosphoenolpyruvate
Yeast
Adenosine
Saccharomyces cerevisiae
Nucleotides
Adenosine Triphosphate
Adenosine Diphosphate
Ribose
Molecular mechanics
Kinetics
Adenine
Mechanics
Hydroxyl Radical
Substrates
Catalytic Domain
Enzymes

ASJC Scopus subject areas

  • Structural Biology
  • Biophysics
  • Biochemistry
  • Molecular Biology

Citar esto

@article{10a6e09f71bd4d9f97b9c6dcf282de0b,
title = "Interaction of adenosine nucleotide analogs with Saccharomyces cerevisiae phosphoenolpyruvate carboxykinase",
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.",
keywords = "Homology modeling, Interaction energy, Nucleotide analog, Phosphoenolpyruvate carboxykinase, Saccharomyces cerevisiae",
author = "Loreto Carrasco and Gonz{\'a}lez, {Fernando D.} and Emilio Cardemil",
year = "1998",
month = "12",
day = "8",
doi = "10.1016/S0167-4838(98)00223-4",
language = "English",
volume = "1429",
pages = "93--101",
journal = "Biochimica et Biophysica Acta - Proteins and Proteomics",
issn = "1570-9639",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Interaction of adenosine nucleotide analogs with Saccharomyces cerevisiae phosphoenolpyruvate carboxykinase

AU - Carrasco, Loreto

AU - González, Fernando D.

AU - Cardemil, Emilio

PY - 1998/12/8

Y1 - 1998/12/8

N2 - 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.

AB - 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.

KW - Homology modeling

KW - Interaction energy

KW - Nucleotide analog

KW - Phosphoenolpyruvate carboxykinase

KW - Saccharomyces cerevisiae

UR - http://www.scopus.com/inward/record.url?scp=0345390047&partnerID=8YFLogxK

U2 - 10.1016/S0167-4838(98)00223-4

DO - 10.1016/S0167-4838(98)00223-4

M3 - Article

C2 - 9920388

AN - SCOPUS:0345390047

VL - 1429

SP - 93

EP - 101

JO - Biochimica et Biophysica Acta - Proteins and Proteomics

JF - Biochimica et Biophysica Acta - Proteins and Proteomics

SN - 1570-9639

IS - 1

ER -