Molecular modeling of the complexes between Saccharomyces cerevisae phosphoenolpyruvate carboxykinase and the ATP analogs pyridoxal 5'- diphosphoadenosine and pyridoxal 5-triphosphoadenosine. Specific labeling of lysine 290

Fernando D. González-Nilo, Rubén Vega, Emilio Cardemil

Resultado de la investigación: Article

3 Citas (Scopus)

Resumen

Molecular mechanics calculations have been employed to obtain models of the complexes between Saccharomyces cerevisiae phosphoenolpyruvate (PEP) kinase and the ATP analogs pyridoxal 5'-diphosphoadenosine (PLP-AMP) and pyridoxal 5'-triphosphoadenosine (PLP-ADP), using the crystalline coordinates of the ATP-pyruvate-Mn2+-Mg2+ complex of Escherichia coli PEP carboxykinase [Tari et al. (1997), Nature Struct. Biol. 4, 990-994]. In these models, the preferred conformation of the pyridoxyl moiety of PLP-ADP and PLP-AMP was established through rotational barrier and simulated annealing procedures. Distances from the carbonyl-C of each analog to ε-N of active- site lysyl residues were calculated for the most stable enzyme-analog complex conformation, and it was found that the closest ε-N is that from Lys290, thus predicting Schiff base formation between the corresponding carbonyl and amino groups. This prediction was experimentally verified through chemical modification of S. cerevisiae PEP carboxykinase with PLP-ADP and PLP-AMP. The results here described demonstrate the use of molecular modeling procedures when planning chemical modification of enzyme-active sites.

Idioma originalEnglish
Páginas (desde-hasta)67-73
Número de páginas7
PublicaciónJournal of Protein Chemistry
Volumen19
N.º1
DOI
EstadoPublished - 2000

Huella dactilar

Phosphoenolpyruvate Carboxykinase (ATP)
Pyridoxal
Administrative data processing
Saccharomyces
Molecular modeling
Adenosinetriphosphate
Labeling
Lysine
Adenosine Monophosphate
Chemical modification
Yeast
Conformations
Enzymes
Saccharomyces cerevisiae
Catalytic Domain
Molecular mechanics
Adenosine Triphosphate
Simulated annealing
Escherichia coli
Phosphoenolpyruvate

ASJC Scopus subject areas

  • Biochemistry

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title = "Molecular modeling of the complexes between Saccharomyces cerevisae phosphoenolpyruvate carboxykinase and the ATP analogs pyridoxal 5'- diphosphoadenosine and pyridoxal 5-triphosphoadenosine. Specific labeling of lysine 290",
abstract = "Molecular mechanics calculations have been employed to obtain models of the complexes between Saccharomyces cerevisiae phosphoenolpyruvate (PEP) kinase and the ATP analogs pyridoxal 5'-diphosphoadenosine (PLP-AMP) and pyridoxal 5'-triphosphoadenosine (PLP-ADP), using the crystalline coordinates of the ATP-pyruvate-Mn2+-Mg2+ complex of Escherichia coli PEP carboxykinase [Tari et al. (1997), Nature Struct. Biol. 4, 990-994]. In these models, the preferred conformation of the pyridoxyl moiety of PLP-ADP and PLP-AMP was established through rotational barrier and simulated annealing procedures. Distances from the carbonyl-C of each analog to ε-N of active- site lysyl residues were calculated for the most stable enzyme-analog complex conformation, and it was found that the closest ε-N is that from Lys290, thus predicting Schiff base formation between the corresponding carbonyl and amino groups. This prediction was experimentally verified through chemical modification of S. cerevisiae PEP carboxykinase with PLP-ADP and PLP-AMP. The results here described demonstrate the use of molecular modeling procedures when planning chemical modification of enzyme-active sites.",
keywords = "Homology modeling, Phosphoenolpyruvate carboxykinase, Pyridoxal 5'- triphosphoadenosine, Pyridoxal 5'-diphosphoadenosine, Rotational energy barrier, Saccharomyces cerevisiae, Simulated annealing",
author = "Gonz{\'a}lez-Nilo, {Fernando D.} and Rub{\'e}n Vega and Emilio Cardemil",
year = "2000",
doi = "10.1023/A:1007099010762",
language = "English",
volume = "19",
pages = "67--73",
journal = "Protein Journal",
issn = "1572-3887",
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number = "1",

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TY - JOUR

T1 - Molecular modeling of the complexes between Saccharomyces cerevisae phosphoenolpyruvate carboxykinase and the ATP analogs pyridoxal 5'- diphosphoadenosine and pyridoxal 5-triphosphoadenosine. Specific labeling of lysine 290

AU - González-Nilo, Fernando D.

AU - Vega, Rubén

AU - Cardemil, Emilio

PY - 2000

Y1 - 2000

N2 - Molecular mechanics calculations have been employed to obtain models of the complexes between Saccharomyces cerevisiae phosphoenolpyruvate (PEP) kinase and the ATP analogs pyridoxal 5'-diphosphoadenosine (PLP-AMP) and pyridoxal 5'-triphosphoadenosine (PLP-ADP), using the crystalline coordinates of the ATP-pyruvate-Mn2+-Mg2+ complex of Escherichia coli PEP carboxykinase [Tari et al. (1997), Nature Struct. Biol. 4, 990-994]. In these models, the preferred conformation of the pyridoxyl moiety of PLP-ADP and PLP-AMP was established through rotational barrier and simulated annealing procedures. Distances from the carbonyl-C of each analog to ε-N of active- site lysyl residues were calculated for the most stable enzyme-analog complex conformation, and it was found that the closest ε-N is that from Lys290, thus predicting Schiff base formation between the corresponding carbonyl and amino groups. This prediction was experimentally verified through chemical modification of S. cerevisiae PEP carboxykinase with PLP-ADP and PLP-AMP. The results here described demonstrate the use of molecular modeling procedures when planning chemical modification of enzyme-active sites.

AB - Molecular mechanics calculations have been employed to obtain models of the complexes between Saccharomyces cerevisiae phosphoenolpyruvate (PEP) kinase and the ATP analogs pyridoxal 5'-diphosphoadenosine (PLP-AMP) and pyridoxal 5'-triphosphoadenosine (PLP-ADP), using the crystalline coordinates of the ATP-pyruvate-Mn2+-Mg2+ complex of Escherichia coli PEP carboxykinase [Tari et al. (1997), Nature Struct. Biol. 4, 990-994]. In these models, the preferred conformation of the pyridoxyl moiety of PLP-ADP and PLP-AMP was established through rotational barrier and simulated annealing procedures. Distances from the carbonyl-C of each analog to ε-N of active- site lysyl residues were calculated for the most stable enzyme-analog complex conformation, and it was found that the closest ε-N is that from Lys290, thus predicting Schiff base formation between the corresponding carbonyl and amino groups. This prediction was experimentally verified through chemical modification of S. cerevisiae PEP carboxykinase with PLP-ADP and PLP-AMP. The results here described demonstrate the use of molecular modeling procedures when planning chemical modification of enzyme-active sites.

KW - Homology modeling

KW - Phosphoenolpyruvate carboxykinase

KW - Pyridoxal 5'- triphosphoadenosine

KW - Pyridoxal 5'-diphosphoadenosine

KW - Rotational energy barrier

KW - Saccharomyces cerevisiae

KW - Simulated annealing

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DO - 10.1023/A:1007099010762

M3 - Article

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AN - SCOPUS:0342656520

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JO - Protein Journal

JF - Protein Journal

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