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: Contribución a una revistaArtículo

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

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  • Bioquímica

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