Mechanism of inactivation of human ribonucleotide reductase with p53R2 by gemcitabine 5′-diphosphate

Biochemistry

Volumn 48, Issue 49, 2009, Pages 11612-11621

  Wang, Jun ^a   Lohman, Gregory J S ^a   Stubbe, JoAnne ^a  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACTIVE SITE; ANTI-CANCER AGENTS; C-TERMINAL TAIL; CLASS I; COVALENTLY BOUND; DIPHOSPHATES; DNA REPAIR; DNA REPLICATIONS; GEMCITABINE; MITOCHONDRIAL DNA; NUCLEOTIDE METABOLISM; QUATERNARY STRUCTURE; RIBONUCLEOTIDE REDUCTASE; S-PHASE; SDS-PAGE ANALYSIS; SEPHADEX; SPECIFIC ACTIVITY;

BRIDGE BEARINGS; CHROMATOGRAPHIC ANALYSIS; DIFFUSERS (OPTICAL); DNA; DRUG PRODUCTS; ENZYME ACTIVITY; GENES; ION EXCHANGE; METABOLISM; NUCLEIC ACIDS; POLYPEPTIDES; PROTEINS; SUGAR (SUCROSE); SUGARS;

SIZE EXCLUSION CHROMATOGRAPHY;

CYTOSINE; GEMCITABINE; RIBONUCLEOTIDE REDUCTASE; SEPHADEX;

ARTICLE; CONTROLLED STUDY; COVALENT BOND; ENZYME INACTIVATION; GEL PERMEATION CHROMATOGRAPHY; MUTANT; NONHUMAN; POLYACRYLAMIDE GEL ELECTROPHORESIS; PRIORITY JOURNAL; PROTEIN ISOLATION; PROTEIN QUATERNARY STRUCTURE;

CELL CYCLE PROTEINS; CHROMATOGRAPHY, GEL; CYTIDINE DIPHOSPHATE; DNA DAMAGE; DNA REPAIR; ENZYME INHIBITORS; HUMANS; MUTAGENESIS, SITE-DIRECTED; PROTEIN SUBUNITS; PROTEIN TRANSPORT; RIBONUCLEOTIDE REDUCTASES;

EID: 71549157751     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi901588z     Document Type: Article

References (52)

1. Stubbe, J., and van der Donk,W.A. (1998) Protein radicals in enzyme catalysis. Chem. Rev. 98, 705-762.
2. Hertel, L. W., Boder, G. B., Kroin, J. S., Rinzel, S. M., Poore, G. A., Todd, G. C., and Grindey, G. B. (1990) Evaluation of the antitumoractivity of gemcitabine (2′,2′-difluoro-2′-deoxycytidine). Cancer Res. 50, 4417-4422.
3. Huang, P., Chubb, S., Hertel, L. W., Grindey, G. B., and Plunkett, W. (1991) Action of 2′,2′-difluorodeoxycytidine on DNA-synthesis. Cancer Res. 51, 6110-6117.
4. Plunkett, W., Huang, P., and Gandhi, V. (1997) Gemcitabine: actions and interactions. Nucleosides Nucleotides 16, 1261-1270.
5. Rivera, F., López-Tarruella, S., Vega-Villegas, M. E., and Salcedo, M. (2009) Treatment of advanced pancreatic cancer: from gemcitabine single agent to combinations and targeted therapy. Cancer Treat. Rev. 35, 335-339.
6. Danesi, R., Altavilla, G., Giovannetti, E., and Rosell, R. (2009) Pharmacogenomics of gemcitabine in non-small-cell lung cancer and other solid tumors. Pharmacogenomics 10, 69-80.
7. Bergman, A. M., Pinedo, H. M., and Peters, G. J. (2002) Determinants of resistance to 2′,2′-difluorodeoxycytidine (gemcitabine). Drug Resist. Updates 5, 19-33.
8. Nordlund, N., and Reichard, P. (2006) Ribonucleotide reductases. Annu. Rev. Biochem. 75, 681-706.
9. Baker, C. H., Banzon, J., Bollinger, J. M., Stubbe, J., Samano, V., Robins, M. J., Lippert, B., Jarvi, E., and Resvick, R. (1991) 2′-deoxy- 2′-methylenecytidine and 2′-deoxy-2′,2′-difluorocytidine 5′-diphosphates-potent mechanism-based inhibitors of ribonucleotide reductase. J. Med. Chem. 34, 1879-1884.
10. van der Donk, W. A., Yu, G. X., Perez, L., Sanchez, R. J., Stubbe, J., Samano, V., and Robins, M. J. (1998) Detection of a new substratederived radical during inactivation of ribonucleotide reductase from Escherichia coli by gemcitabine 5′-diphosphate. Biochemistry 37, 6419-6426. (Pubitemid 28213662)
11. Wang, J., Lohman, G. J., and Stubbe, J. (2007) Enhanced subunit interactions with gemcitabine-5′-diphosphate inhibit ribonucleotide reductases. Proc. Natl. Acad. Sci. U.S.A. 104, 14324-14329.
12. Artin, E., Wang, J., Lohman,G. J. S., Yokoyama, K., Yu, G., Griffin, R. G., Barr, G., and Stubbe, J. (2009) Insight into the mechanism of inactivation of ribonucleotide reductase by gemcitabine 5′-diphosphate in the presence and absence of reductant, Biochemistry (DOI 10.1021/bi901590q).
13. Kashlan, O. B., and Cooperman, B. S. (2003) Comprehensive model for allosteric regulation of mammalian ribonucleotide reductase: refinements and consequences. Biochemistry 42, 1696-1706. (Pubitemid 36205978)
14. Rofougaran, R., Vodnala, M., and Hofer, A. (2006) Enzymatically active mammalian ribonucleotide reductase exists primarily as an alpha(6)beta(2) octamer. J. Biol. Chem. 281, 27705-27711.
15. Sjöberg, B. M., and Reichard, P. (1977) Nature of free-radical in ribonucleotide reductase from Escherichia coli. J. Biol. Chem. 252, 536-541.
16. Sjöberg, B. M., Reichard, P., Gräslund, A., and Ehrenberg, A. (1978) The tyrosine free radical in ribonucleotide reductase from Escherichia coli. J. Biol. Chem. 253, 6863-6865.
17. Tanaka, H., Arakawa, H., Yamaguchi, T., Shiraishi, K., Fukuda, S., Matsui, K., Takei, Y., and Nakamura, Y. (2000) A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. Nature 404, 42-49. (Pubitemid 30143125)
18. Nakano, K., Balint, E., Ashcroft, M., and Vousden, K. H. (2000) A ribonucleotide reductase gene is a transcriptional target of p53 and p73. Oncogene 19, 4283-4289. (Pubitemid 30750926)
19. Pontarin, G., Fijolek, A., Pizzo, P., Ferraro, P., Rampazzo, C., Pozzan, T., Thelander, L., Reichard, P. A., and Bianchi, V. (2008) Ribonucleotide reduction is a cytosolic process in mammalian cells independently of DNA damage. Proc. Natl. Acad. Sci. U.S.A. 105, 17801-17806.
20. Yamaguchi, T., Matsuda, K., Saqiya, Y., Iwadate, M., Fujino, M. A., Nakamura, Y., and Arakawa, H. (2001) p53R2-dependent pathway for DNA synthesis in a p53-regulated cell cycle checkpoint. Cancer Res. 61, 8256-8262. (Pubitemid 33091620)
21. Xue, L., Zhou, B., Liu, X., Qiu, W., Jin, Z., and Yen, Y. (2003) Wild-type p53 regulates human ribonucleotide reductase by protein-protein interaction with p53R2 as well as hRRM2 subunits. Cancer Res. 63, 980-986. (Pubitemid 36278428)
22. Bourdon, A., Minai, L., Serre, V., Jais, J., Sarzi, E., Aubert, S., Chretien, D., Lonlay, P., Paquis-fluckinger, V., Arakawa, H., Nakamura, Y., Munnich, A., and Rötig, A. (2007) Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion. Nat. Genet. 39, 776-780.
23. Chang, L., Zhou, B., Hu, S., Guo, R., Liu, X., Jones, S. N., and Yen, Y. (2008) ATM-mediated serine 72 phosphorylation stabilizes ribonucleotide reductase small subunit p53R2 protein against MDM2 to DNA damage. Proc. Natl. Acad. Sci. U.S.A. 105, 18519-18524.
24. Piao, C., Jin, M., Kim, H. B., Lee, S. M., Amatya, P. N., Hyun, J. W., Chang, I. Y., and You, H. J. (2009) Ribonucleotide reductase small subunit p53R2 suppresses MEK-EPK activity by binding to ERK kinase 2. Oncogene 28, 2173-2184.
25. Shao, J. M., Zhou, B. S., Zhu, L. J., Qiu, W. H., Yuan, Y. C., Xi, B. X., and Yen, Y. (2004) In vitro characterization of enzymatic properties and inhibition of the p53R2 subunit of human ribonucleotide reductase. Cancer Res. 64, 1-6.
26. Guittet, O., Håkansson, P., Voevodskaya, N., Fridd, S., Gräslund, A., Arakawa, H., Nakamura, Y., and Thelander, L. (2001) Mammalian p53R2 protein forms an active ribonucleotide reductase in vitro with the R1 protein, which is expressed both in resting cells in response to DNA damage and in proliferating cells. J. Biol. Chem. 276, 40647-40651.
27. Liu, X., Xue, L., and Yen, Y. (2008) Redox property of ribonucleotide reductase small subunit M2 and p53R2. Methods Mol. Biol. 477, 195-206.
28. Silva, D. J., Stubbe, J., Samano, V., and Robins, M. J. (1998) Gemcitabine 5′-triphosphate is a stoichiometric mechanism-based inhibitor of Lactobacillus leichmannii ribonucleoside triphosphate reductase: Evidence for thiyl radical-mediated nucleotide radical formation. Biochemistry 37, 5528-5535. (Pubitemid 28241935)
29. 2CTP: covalent modification (part I), Biochemistry (manuscript in preparation).
30. 2CTP: adenosylcobalamin destruction and formation of a nucleotide based radical, Biochemistry (manuscript in preparation).
31. Stubbe, J., and van der Donk, W. A. (1995) Ribonucleotide reductases: radical enzymes with suicidal tendencies. Chem. Biol. 12, 793-801.
32. Wang, X., Zhenchuk, A., Wiman, K. G., and Albertioni, F. (2009) Regulation of p53R2 and its role as potential target for cancer therapy. Cancer Lett. 276, 1-7.
33. Lunn, C. A., Kathju, S., Wallace, B. J., Kushner, S. R., and Pigiet, V. (1984) Amplification and purification of plasmid-encoded thioredoxin from Escherichia coli K12. J. Biol. Chem. 259, 469-474.
34. Russel, M., and Model, P. (1985) Direct cloning of the trxB gene that encodes thioredoxin reductase. J. Bacteriol. 163, 238-242. (Pubitemid 15012742)
35. Parkin, S. E., Chen, S., Ley, B. A., Mangravite, L., Edmondson, D. E., Huynh, B. H., and Bollinger, J. M.Jr. (1998) Electron injection through a specific pathway determines the outcome of oxygen activation at the diiron cluster in the F208Y mutant of Escherichia coli ribonucleotide reductase protein R2. Biochemistry 37, 1124-1130. (Pubitemid 28100615)
36. Berglund, O., and Eckstein, F. (1974) ATP- and dATP-substituted agaroses and the purification of ribonucleotide reductases. Methods Enzymol. 34, 253-261.
37. Perlstein, D. L., Ge, J., Ortigosa, A. D., Robblee, J. H., Zhang, Z., Huang, M., and Stubbe, J. (2005) The active form of the Saccharomyces cerevisiae ribonucleotide reductase small subunit is a heterodimer in vitro and in vivo. Biochemistry 44, 15366-15377. (Pubitemid 41681471)
38. Steeper, J. R., and Steuart, C. C. (1970) A rapid assay for CDP reductase activity in mammalian cell extracts. Anal. Biochem. 34, 123-130.
39. Salowe, S. P., and Stubbe, J. (1986) Cloning, overproduction, and purification of the B2 subunit of ribonucleoside-diphosphate reductase. J. Bacteriol. 165, 363-366. (Pubitemid 16060500)
40. Ortigosa, A. D., Hristova, D., Perlstein, D. L., Zhang, Z., Huang, M. X., and Stubbe, J. (2006) Determination of the in vivo stoichiometry of tyrosyl radical per beta beta′ in Saccharomyces cerevisiae ribonucleotide reductase. Biochemistry 45, 12282-12294. (Pubitemid 44527551)
41. Hristova, D., Wu, C. H., Jiang, W., Krebs, C., and Stubbe, J. (2008) Importance of the maintenance pathway in the regulation of the activity of Escherichia coli ribonucleotide reductase. Biochemistry 47, 3989-3999.
42. van der Donk, W. A., Yu, G., Silva, D. J., and Stubbe, J. (1996) Inactivation of ribonucleotide reductase by (E)-2′-fluoromethylene- 2′-deoxycytidine 5′-diphosphate: a paradigm for nucleotide mechanism based inhibitors. Biochemistry 35, 8381-8391. (Pubitemid 26234943)
43. Zipse, H., Artin, E., Wnuk, S., Lohman, G. J., Martino, D., Griffin, R. G., Kacprzak, S., Kaupp, M., Hoffman, B., Bennati, M., Stubbe, J., and Lees, N. (2009) Stucture of the nucleotide radical formed during reaction of CDP/TTP with the E441Q-α2β2 of E. coli ribonucleotide reductase. J. Am. Chem. Soc. 131, 200-211.
44. Xu, H., Faber, C., Uchiki, T., Racca, J., and Dealwis, C. (2006) Structures of eukaryotic ribonucleotide reductase I define gemcitabine diphosphate binding and subunit assembly. Proc. Natl. Acad. Sci. U.S.A. 103, 4028-4033.
45. Mao, S. S., Johnston, M. I., Bollinger, J. M., and Stubbe, J. (1989) Mechanism-based inhibition of a mutant Escherichia coli ribonucleotide reductase (cysteine-225-serine) by its substrate CDP. Proc. Natl. Acad. Sci. U.S.A. 86, 1485-1489.
46. Mao, S. S., Holler, T. P., Bollinger, J. M.Jr., Yu, G. X., Johnston,M. I., and Stubbe, J. (1992) Interaction of C225SR1 mutant subunit of ribonucleotide reductase with R2 and nucleoside diphosphates: tales of a suicidal enzyme. Biochemistry 31, 9744-9751.
47. Mao, S. S., Holler, T. P., Yu, G. X., Bollinger, J. M., Booker, S., Johnston, M. I., and Stubbe, J. (1992) A model for the role of multiple cysteine residues involved in ribonucleotide reduction: amazing and still confusing. Biochemistry 31, 9733-9743.
48. Lin, A. N. I., Ashley, G. W., and Stubbe, J. (1987) Location of the redox-active thiols of ribonucleotide reductase: sequence similarity between the Escherichia coli and Lactobacillus leichmannii enzymes. Biochemistry 26, 6905-6909.
49. Eriksson, H. K. (2001) Kinetics in the pre-steady state of the formation of cystines in ribonucleoside diphosphate reductase: evidence for an asymmetric complex. Biochemistry 40, 9631-9637.
50. Zhang, Z., Yang, K., Chen, C., Feser, J., and Huang, M. (2007) Role of the C terminus of the ribonucleotide reductase large subunit in enzyme regeneration and its inhibition by Sml1. Proc. Natl. Acad. Sci. U.S.A. 104, 2217-2222.
51. Ge, J., Yu, G. X., Ator, M. A., and Stubbe, J. (2003) Pre-steady-state and steady-state kinetic analysis of E. coli class I ribonucleotide reductase. Biochemistry 42, 10071-10083. (Pubitemid 37052027)
52. Uppsten, M., Färnegårdh, M., Domkin, V., and Uhlin, U. (2006) The first holocomplex structure of ribonucleotide reductase gives new insight into its mechanism of action. J. Mol. Biol. 359, 365-377.