| Autor: |
Barbara Z. Eletskaya, Anton F. Mironov, Ilya V. Fateev, Maria Ya. Berzina, Konstantin V. Antonov, Olga S. Smirnova, Alexandra B. Zatsepina, Alexandra O. Arnautova, Yulia A. Abramchik, Alexander S. Paramonov, Alexey L. Kayushin, Anastasia L. Khandazhinskaya, Elena S. Matyugina, Sergey N. Kochetkov, Anatoly I. Miroshnikov, Igor A. Mikhailopulo, Roman S. Esipov, Irina D. Konstantinova |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Biomolecules, Vol 14, Iss 7, p 798 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2218-273X |
| DOI: |
10.3390/biom14070798 |
| Popis: |
Enzymatic transglycosylation of the fleximer base 4-(4-aminopyridine-3-yl)-1H-pyrazole using recombinant E. coli purine nucleoside phosphorylase (PNP) resulted in the formation of “non-typical” minor products of the reaction. In addition to “typical” N1-pyrazole nucleosides, a 4-imino-pyridinium riboside and a N1-pyridinium-N1-pyrazole bis-ribose derivative were formed. N1-Pyrazole 2′-deoxyribonucleosides and a N1-pyridinium-N1-pyrazole bis-2′-deoxyriboside were formed. But 4-imino-pyridinium deoxyriboside was not formed in the reaction mixture. The role of thermodynamic parameters of key intermediates in the formation of reaction products was elucidated. To determine the mechanism of binding and activation of heterocyclic substrates in the E. coli PNP active site, molecular modeling of the fleximer base and reaction products in the enzyme active site was carried out. As for N1-pyridinium riboside, there are two possible locations for it in the PNP active site. The presence of a relatively large space in the area of amino acid residues Phe159, Val178, and Asp204 allows the ribose residue to fit into that space, and the heterocyclic base can occupy a position that is suitable for subsequent glycosylation. Perhaps it is this “upside down” arrangement that promotes secondary glycosylation and the formation of minor bis-riboside products. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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