Thermophilic nucleoside phosphorylases: Their properties, characteristics and applications

Kamel, Sarah; Thiele, Isabel; Neubauer, Peter; Wagner, Anke

doi:10.1016/j.bbapap.2019.140304

Cited by 29 publications

(25 citation statements)

References 45 publications

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“…22 MTAP is reported to function as a trimer in all species except Sulfolobus solfataricus, 23 in which it functions as a hexamer and catalyzes the phosphorolysis of inosine, guanosine, and adenosine. 24 Compared with the NP-I family, TP (EC 2.4.2.4) and pyrimidine nucleoside phosphorylases (PyNPs; EC 2.4.2.2) belong to the NP-II family and function as a dimer in all cases 1,25,26 (Figure S3).…”

Section: Ppnp Lack the Divalent Metal-binding Sitementioning

confidence: 99%

Crystal structures of a new class of pyrimidine/purine nucleoside phosphorylase revealed a Cupin fold

Wen

Guo

et al. 2022

Proteins

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Nucleotides metabolism is a fundamental process in all organisms. Two families of nucleoside phosphorylases (NP) that catalyze the phosphorolytic cleavage of the glycosidic bond in nucleosides have been found, including the trimeric or hexameric NP‐I and dimeric NP‐II family enzymes. Recent studies revealed another class of NP protein in Escherichia coli named Pyrimidine/purine nucleoside phosphorylase (ppnP), which can catalyze the phosphorolysis of diverse nucleosides and yield d‐ribose 1‐phosphate and the respective free bases. Here, we solved the crystal structures of ppnP from E. coli and the other three species. Our studies revealed that the structure of ppnP belongs to the RlmC‐like Cupin fold and showed as a rigid dimeric conformation. Detail analysis revealed a potential nucleoside binding pocket full of hydrophobic residues, and the residues involved in the dimer and pocket formation are all well conserved in bacteria. Since the Cupin fold is a large superfamily in the biosynthesis of natural products, our studies provide the structural basis for understanding, and the directed evolution of NP proteins.

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Section: Ppnp Lack the Divalent Metal-binding Sitementioning

confidence: 99%

Crystal structures of a new class of pyrimidine/purine nucleoside phosphorylase revealed a Cupin fold

Wen

Guo

et al. 2022

Proteins

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“…MTAP is reported to function as a trimer in all species except Sulfolobus solfataricus 22 , in which it functions as a hexamer and catalyzes the phosphorolysis of inosine, guanosine, and adenosine 23 . Compared with the NP-I family, TP (EC 2.4.2.4) and pyrimidine nucleoside phosphorylases (PyNPs; EC 2.4.2.2) belong to the NP-II family and function as a dimer in all cases 1,24,25 . Our structure studies revealed that the ppnP family proteins showed dimeric quaternary conformations like NP-II class, but with a different dimerization mode belonging to the cupin fold.…”

Section: Ppnp Lack the Divalent Metal-binding Sitementioning

confidence: 99%

Crystal structures of a new class of pyrimidine/purine nucleoside phosphorylase (ppnP) revealed a Cupin fold

Wen

Guo

et al. 2021

Preprint

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Nucleotides metabolism is a fundamental process in all organisms. Two families of nucleoside phosphorylases (NP) that catalyze the phosphorolytic cleavage of the glycosidic bond in nucleosides have been found, including the trimeric or hexameric NP-I and dimeric NP-II family enzymes. Recently studies revealed another class of NP protein in E. coli named Pyrimidine/purine nucleoside phosphorylase (ppnP), which can catalyze the phosphorolysis of diverse nucleosides and yield D-ribose 1-phosphate and the respective free bases. Here, we solve the crystal structures of ppnP from E. coli and the other three species. Our studies revealed that the structure of ppnP belongs to the Rlmc-like cupin fold and showed as a rigid dimeric conformation. Detail analysis revealed a potential nucleoside binding pocket full of hydrophobic residues. And the residues involved in the dimer and pocket formation are all well conserved in bacteria. Since the cupin fold is a large superfamily in the biosynthesis of natural products, our studies provide the structural basis for understanding and the directed evolution of NP proteins.

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“…Tubercidine (7-deazaadenosine) is a known antibiotic and an inhibitor of the bacterial (hexameric) forms of PNP [12]. It is also a substrate of some thermostable bacterial PNPs at higher temperatures [29,30]. The reaction of tubercidine and 2 -deoxytubercidine with chloroacetaldehyde gives the respective 1,N 6 -etheno derivatives in good yields [24,25].…”

Section: Properties Of 1n 2 -Etheno-tubercidinementioning

confidence: 99%

Tricyclic Nucleobase Analogs and Their Ribosides as Substrates and Inhibitors of Purine-Nucleoside Phosphorylases III. Aminopurine Derivatives

Stachelska-Wierzchowska

Wierzchowski

Górka

et al. 2020

Molecules

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Etheno-derivatives of 2-aminopurine, 2-aminopurine riboside, and 7-deazaadenosine (tubercidine) were prepared and purified using standard methods. 2-Aminopurine reacted with aqueous chloroacetaldehyde to give two products, both exhibiting substrate activity towards bacterial (E. coli) purine-nucleoside phosphorylase (PNP) in the reverse (synthetic) pathway. The major product of the chemical synthesis, identified as 1,N2-etheno-2-aminopurine, reacted slowly, while the second, minor, but highly fluorescent product, reacted rapidly. NMR analysis allowed identification of the minor product as N2,3-etheno-2-aminopurine, and its ribosylation product as N2,3-etheno-2-aminopurine-N2-β-d-riboside. Ribosylation of 1,N2-etheno-2-aminopurine led to analogous N2-β-d-riboside of this base. Both enzymatically produced ribosides were readily phosphorolysed by bacterial PNP to the respective bases. The reaction of 2-aminopurine-N9-β -d-riboside with chloroacetaldehyde gave one major product, clearly distinct from that obtained from the enzymatic synthesis, which was not a substrate for PNP. A tri-cyclic 7-deazaadenosine (tubercidine) derivative was prepared in an analogous way and shown to be an effective inhibitor of the E. coli, but not of the mammalian enzyme. Fluorescent complexes of amino-purine analogs with E. coli PNP were observed.

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Thermophilic nucleoside phosphorylases: Their properties, characteristics and applications

Cited by 29 publications

References 45 publications

Crystal structures of a new class of pyrimidine/purine nucleoside phosphorylase revealed a Cupin fold

Crystal structures of a new class of pyrimidine/purine nucleoside phosphorylase revealed a Cupin fold

Crystal structures of a new class of pyrimidine/purine nucleoside phosphorylase (ppnP) revealed a Cupin fold

Tricyclic Nucleobase Analogs and Their Ribosides as Substrates and Inhibitors of Purine-Nucleoside Phosphorylases III. Aminopurine Derivatives

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