Recognition of Artificial Nucleobases byE. coliPurine Nucleoside Phosphorylase versus its Ser90Ala Mutant in the Synthesis of Base-Modified Nucleosides
| Autor: | Maria I. Kharitonova, Vasily N. Stepanenko, Anatoly I. Miroshnikov, Ilja V. Fateev, Konstantin V. Antonov, Igor A. Mikhailopulo, Roman S. Esipov, Irina D. Konstantinova, Yuri A. Sokolov, Frank Seela, Vladimir A. Stepchenko, Kartik Temburnikar, Katherine L. Seley-Radtke |
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| Rok vydání: | 2015 |
| Předmět: |
Benzimidazole
Stereochemistry Purine analogue Purine nucleoside phosphorylase Crystallography X-Ray medicine.disease_cause Catalysis Nucleobase Dephosphorylation Structure-Activity Relationship chemistry.chemical_compound Escherichia coli medicine chemistry.chemical_classification Alanine Binding Sites Base Sequence Organic Chemistry Nucleosides General Chemistry Benzoxazole Kinetics Enzyme Purine-Nucleoside Phosphorylase chemistry Biochemistry |
| Zdroj: | Chemistry - A European Journal. 21:13401-13419 |
| ISSN: | 0947-6539 |
| Popis: | A wide range of natural purine analogues was used as probe to assess the mechanism of recognition by the wild-type (WT) E. coli purine nucleoside phosphorylase (PNP) versus its Ser90Ala mutant. The results were analyzed from viewpoint of the role of the Ser90 residue and the structural features of the bases. It was found that the Ser90 residue of the PNP 1) plays an important role in the binding and activation of 8-aza-7-deazapurines in the synthesis of their nucleosides, 2) participates in the binding of α-D-pentofuranose-1-phosphates at the catalytic site of the PNP, and 3) catalyzes the dephosphorylation of intermediary formed 2-deoxy-α-D-ribofuranose-1-phosphate in the trans-2-deoxyribosylation reaction. 5-Aza-7-deazaguanine manifested excellent substrate activity for both enzymes, 8-amino-7-thiaguanine and 2-aminobenzothiazole showed no substrate activity for both enzymes. On the contrary, the 2-amino derivatives of benzimidazole and benzoxazole are substrates and are converted into the N1- and unusual N2-glycosides, respectively. 9-Deaza-5-iodoxanthine showed moderate inhibitory activity of the WT E. coli PNP, whereas 9-deazaxanthine and its 2'-deoxyriboside are weak inhibitors. |
| Databáze: | OpenAIRE |
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