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Structural Basis for Substrate Specificity of Escherichia coli Purine Nucleoside Phosphorylase*
TLDR
These studies explain the preference of the enzyme for ribose sugars, show increased flexibility for active site residues Asp204 and Arg24, and suggest that interactions involving the 1- and 6-positions of the purine and the 4′- and 5′-pos positions of the ribose provide the best opportunities to increase prodrug specificity and enzyme efficiency.
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Tumor cell bystander killing in colonic carcinoma utilizing the Escherichia coli DeoD gene to generate toxic purines.
TLDR
A rational approach is established to achieve significant bystander killing, even after gene transfer to only a small fraction of tumor cells, after treatment with 6-methyl-purine-2'-deoxyribonucleoside, a deoxyadenosine analog that is a substrate for E. coli PNP but not human PNP.
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Metabolism and metabolic actions of 6-methylpurine and 2-fluoroadenine in human cells.
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The crystal structure of Streptococcus pyogenes uridine phosphorylase reveals a distinct subfamily of nucleoside phosphorylases.
TLDR
Biochemical studies of wild-type SpUP showed that its substrate specificity is similar to that of EcUP, while EcUP is ∼7-fold more efficient than SpUP, suggesting that the negative charge in the transition state resides mostly on uracil O2, in contrast to EcUP for which transition state stabilization occurs mostly at O4.
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6-Methylthioguanylic acid, a metabolite of 6-thioguanine.
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Metabolism and Metabolic Effects of Halopurine Nucleosides in Tumor Cells in Culture
Abstract Within a series of halo derivatives of adenosine, deoxyadenosine and arabinosyladenine attempts have been made to correlate structure with cytotoxicity, substrate activity for adenosine…
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Novel DNA methyltransferase-1 (DNMT1) depleting anticancer nucleosides, 4′-thio-2′-deoxycytidine and 5-aza-4′-thio-2′-deoxycytidine
TLDR
Data show that 4′-thio modified dCyd analogs, such as T-dCyd or aza-T-DCyd, could be a new source of clinically effective DNMT1 depleting anticancer compounds with less toxicity.
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Role of methylthioadenosine/S-adenosylhomocysteine nucleosidase in Vibrio cholerae cellular communication and biofilm development.
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Purine ribonucleoside kinase activity and resistance to some analogs of adenosine.
TLDR
Results indicate that adenosine kinase is an enzyme essential for the activation of many cytotoxic nucleoside and that loss of this enzyme activity is a mechanism of resistance to these nucleosides.
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Formation and significance of 6-methylthiopurine ribonucleotide as a metabolite of 6-mercaptopurine.
TLDR
It is likely that 6-MeMP ribonucleotide is responsible for most or all of the inhibition of de novo purine synthesis produced by 6-MP, as well as being an inhibitor of phosphoribosyl pyrophosphate amidotransferase.
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