Phospho-ribosyl transferase

The second example in Figure 11.2 shows guanine bound to a phospho-ribosyl transferase. Only one of the two possible tautomers is able to form the correct hydrogen bond to an active site aspartate. 

Fig. 11.2 Guanine bound to a phospho-ribosyl transferase (PDB la95).

Fig. lA. Anabolic and catabolic pathways of 5-FU. DPD dihydropyrimidine dehydrogenase, DP di-hydropyrimidinase, pUP beta-ureidopropionase, UP uridine phosphorylase, OPRT orotate phospho-ribosyl transferase, UK uridine kinase, TP thymidine phosphorylase, TK thymidine kinase, RNR ribonucleotide reductase. The three active metabolites (shown in rectangles) are FdUMP (5-fluoro-2 -deoxyuridine 5 -monophosphate) inhibiting TS (thymidylate synthase), and FUTP (5-fluorouridine 5 -triphosphate) and FdUTP (5-fluoro 2 -deoxyuridine 5 -triphosphate) interfering with RNA and DNA, respectively. 

Hirsch, and A.W. Hsie. A quantitative assay of mutation induction at hypoxanthine-guanine phospho-ribosyl transferase locus in Chinese hamster ovary cells (CHO/HGPRT system) Development and definition of the system. Mutat. Res. 45 91-101, 1977. 

Bl. Bakay, B., and Nyhan, W. L., Heterogeneity of hypoxanthine guanine phospho-ribosyl transferase from human erythrocytes. Arch. Biochem. Biophys. 168, 26-34... 

Guanine phospho-ribosyl transferase n 6/4/52 [xM (IC50) Aronov, A.M. et at, Antimicr. Agents Chemother. 2001, 45,2571. 

Neither transfer of single ADPR residues by specific eukaryotic transferases nor the existence of other than ester-type linkages in ADPR protein conjugates were recognized for a number of years [24]. Now, there is increasing evidence that the eukaryotic cell possesses a rather elaborate instrumentarium of ADP-ribosylation reactions to modulate important processes. The use of mono(ADPR) groups for the covalent modification of protein provides a tool that may prove to be as versatile as poly(ADP-ribosyl)ation. In addition to the systems discussed here (alkylated cells, differentiation, tumor promotors), mono(ADP-ribosyl)ation may be involved also in the modulation of protein synthesis [8], in the response to heat shock (M. Jacobson, personal communication), and in glutamine synthesis [25]. Nonenzymic mono(ADP-ribosyl)ation reactions must also be taken into consideration whenever the functions of active (P)ADP-ribose as present in the pyridine nucleotides are studied. Finally, preliminary data may indicate that an additional way to modulate protein functions could be provided by phospho-(ADP-ribosylation) reactions. 

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