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Research Article: The N‐Terminal Domain of 2′,3′‐Cyclic Nucleotide 3′‐Phosphodiesterase Harbors a GTP/ATP Binding Site
Author(s) -
Stingo Stefania,
Masullo Mariorosario,
Polverini Eugenia,
Laezza Chiara,
Ruggiero Immacolata,
Arcone Rosaria,
Ruozi Enrica,
Piaz Fabrizio Dal,
Malfitano Anna Maria,
D’Ursi Anna Maria,
Bifulco Maurizio
Publication year - 2007
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2007.00592.x
Subject(s) - nucleotide , cyclic nucleotide phosphodiesterase , phosphodiesterase , cyclic nucleotide binding domain , purine , biochemistry , cyclic nucleotide , chemistry , gtp' , guanine nucleotide exchange factor , guanine , stereochemistry , gtpase , enzyme , gene
The interaction between 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase and guanine/adenine nucleotides was investigated. The binding of purine nucleotides to 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase was revealed by both direct and indirect methods. In fact, surface plasmon resonance experiments, triphosphatase activity measurements, and fluorescence experiments revealed that 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase binds purine nucleotide triphosphates with an affinity higher than that displayed for diphosphates; on the contrary, the affinity for both purine monophosphates and pyrimidine nucleotides was negligible. An interpretation of biological experimental data was achieved by a building of 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase N‐terminal molecular model. The structural elements responsible for nucleotide binding were identified and potential complexes between the N‐terminal domain of CNP‐ase and nucleotide were analyzed by docking simulations. Therefore, our findings suggest new functional and structural property of the N‐terminal domain of CNPase.