Crystal structure, biochemical and cellular activities demonstrate separate functions of MTH1 and MTH2

Nature Communications

Volumn 6, Issue , 2015, Pages

  Carter, Megan ^a   Jemth, Ann Sofie ^b   Hagenkort, Anna ^b   Page, Brent D G ^b   Gustafsson, Robert ^a   Griese, Julia J ^a   Gad, Helge ^b   Valerie, Nicholas C K ^b   Desroses, Matthieu ^b   Boström, Johan ^b   Warpman Berglund, Ulrika ^b   Helleday, Thomas ^b   Stenmark, Pål ^a  

^a STOCKHOLM UNIVERSITY   (Sweden)

^b SCIENCE FOR LIFE LABORATORY   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

BACTERIAL DNA; BACTERIAL PROTEIN; MTH1 PROTEIN; MTH2 PROTEIN; NUDIX HYDROLASE; NUDT15 PROTEIN; NUDT17 PROTEIN; NUDT18 PROTEIN; PYROPHOSPHORIC ACID DERIVATIVE; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; 8-OXODEOXYGUANOSINE TRIPHOSPHATE; 8-OXODGTPASE; DEOXYGUANOSINE PHOSPHATE; DEOXYRIBONUCLEOTIDE; DNA LIGASE; INORGANIC PYROPHOSPHATASE; MTH2 PROTEIN, HUMAN; PHOSPHATASE;

BIOCHEMICAL COMPOSITION; CELLS AND CELL COMPONENTS; CRYSTAL STRUCTURE; ENZYME ACTIVITY; HOMOLOGY; METABOLISM; OXIDATION; REDOX POTENTIAL; SUBSTRATE;

A375 CELL LINE; ALKALINITY; ARTICLE; BINDING SITE; BIOCHEMICAL ANALYSIS; CANCER CELL LINE; CELL ACTIVITY; CELL SURVIVAL; CONTROLLED STUDY; CRYSTAL STRUCTURE; DNA DAMAGE; EMBRYO; ENZYME ACTIVITY; FEMALE; GENE SILENCING; HCT116 CELL LINE; HELA CELL LINE; HUMAN; HUMAN CELL; HYDROGEN BOND; IN VITRO STUDY; KINETIC PARAMETERS; MCF 7 CELL LINE; MOLECULAR RECOGNITION; NONHUMAN; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN HYDROLYSIS; PROTEIN LOCALIZATION; PROTEIN STRUCTURE; U2OS CELL LINE; CHEMISTRY; CRYSTALLIZATION; ENZYME SPECIFICITY; HCT 116 CELL LINE; MCF-7 CELL LINE; METABOLISM; OXIDATION REDUCTION REACTION; OXIDATIVE STRESS; TUMOR CELL LINE; WESTERN BLOTTING;

BACTERIA (MICROORGANISMS);

BLOTTING, WESTERN; CELL LINE, TUMOR; CELL SURVIVAL; CRYSTALLIZATION; DEOXYGUANINE NUCLEOTIDES; DEOXYRIBONUCLEOTIDES; DNA REPAIR ENZYMES; HCT116 CELLS; HELA CELLS; HUMANS; MCF-7 CELLS; OXIDATION-REDUCTION; OXIDATIVE STRESS; PHOSPHORIC MONOESTER HYDROLASES; PYROPHOSPHATASES; SUBSTRATE SPECIFICITY;

EID: 84938634251     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms8871     Document Type: Article

References (38)

1. Cheung-Ong, K., Giaever, G. & Nislow, C. DNA-damaging agents in cancer chemotherapy: serendipity and chemical biology. Chem. Biol. 20, 648-659 (2013).
2. Bouwman, P. & Jonkers, J. The effects of deregulated DNA damage signalling on cancer chemotherapy response and resistance. Nat. Rev. Cancer 12, 587-598 (2012).
3. Fu, D., Calvo, J. A. & Samson, L. D. Balancing repair and tolerance of DNA damage caused by alkylating agents. Nat. Rev. Cancer 12, 104-120 (2012).
4. Rai, P. et al. Enhanced elimination of oxidized guanine nucleotides inhibits oncogenic RAS-induced DNA damage and premature senescence. Oncogene 30, 1489-1496 (2011).
5. Zhang, Y. et al. Redox control of the survival of healthy and diseased cells. Antioxid. Redox Signal 15, 2867-2908 (2011).
6. Topal, M. D. & Baker, M. S. DNA precursor pool: a significant target for N-methyl-N-nitrosourea in C3H/10T1/2 clone 8 cells. Proc. Natl Acad. Sci. USA 79, 2211-2215 (1982).
7. Maki, H. & Sekiguchi, M. MutT protein specifically hydrolyses a potent mutagenic substrate for DNA synthesis. Nature 355, 273-275 (1992).
8. Bessman, M. J., Frick, D. N. & O'Handley, S. F. The MutT proteins or 'Nudix' hydrolases, a family of versatile, widely distributed, 'housecleaning' enzymes. J. Biol. Chem. 271, 25059-25062 (1996).
9. Furuichi, M. et al. Genomic structure and chromosome location of the human mutT homologue gene MTH1 encoding 8-oxo-dGTPase for prevention of A:T to C:G transversion. Genomics 24, 485-490 (1994).
10. Cai, J. P., Ishibashi, T., Takagi, Y., Hayakawa, H. & Sekiguchi, M. Mouse MTH2 protein which prevents mutations caused by 8-oxoguanine nucleotides. Biochem. Biophys. Res. Commun. 305, 1073-1077 (2003).
11. Hori, M., Satou, K., Harashima, H. & Kamiya, H. Suppression of mutagenesis by 8-hydroxy-2'-deoxyguanosine 5'-triphosphate (7, 8-dihydro-8-oxo-2'-deoxyguanosine 5'-triphosphate) by human MTH1, MTH2, and NUDT5. Free Radic. Biol. Med. 48, 1197-1201 (2010).
12. Takagi, Y. et al. Human MTH3 (NUDT18) protein hydrolyzes oxidized forms of guanosine and deoxyguanosine diphosphates comparison with MTH1 and MTH2. J. Biol. Chem. 287, 21541-21549 (2012).
13. Gad, H. et al. MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool. Nature 508, 215-221 (2014).
14. Nagy, G. N., Leveles, I. & Vertessy, B. G. Preventive DNA repair by sanitizing the cellular (deoxy)nucleoside triphosphate pool. FEBS J. 281, 4207-4223 (2014).
15. Nakabeppu, Y. Cellular levels of 8-oxoguanine in either DNA or the nucleotide pool play pivotal roles in carcinogenesis and survival of cancer cells. Int. J. Mol. Sci. 15, 12543-12557 (2014).
16. Tsuzuki, T. et al. Spontaneous tumorigenesis in mice defective in the MTH1 gene encoding 8-oxo-dGTPase. Proc. Natl Acad. Sci. USA 98, 11456-11461 (2001).
17. Fujikawa, K. et al. The oxidized forms of dATP are substrates for the human MutT homologue, the hMTH1 protein. J. Biol. Chem. 274, 18201-18205 (1999).
18. Krissinel, E. & Henrick, K. Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774-797 (2007).
19. Svensson, L. M. et al. Crystal structure of human MTH1 and the 8-oxo-dGMP product complex. FEBS Lett. 585, 2617-2621 (2011).
20. Yang, J. J. et al. Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia. J. Clin. Oncol. 33, 1235-1242 (2015).
21. Yang, S. K. et al. A common missense variant in NUDT15 confers susceptibility to thiopurine-induced leukopenia. Nat. Genet. 46, 1017-1020 (2014).
22. Huber, K. V. et al. Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy. Nature 508, 222-227 (2014).
23. Sakai, Y. et al. A molecular basis for the selective recognition of 2-hydroxy-dATP and 8-oxo-dGTP by human MTH1. J. Biol. Chem. 277, 8579-8587 (2002).
24. Arimori, T. et al. Diverse substrate recognition and hydrolysis mechanisms of human NUDT5. Nucleic Acids Res. 39, 8972-8983 (2011).
25. Kabsch, W. XDS. Acta. Crystallogr. D. Biol. Crystallogr. 66, 125-132 (2010).
26. Winn, M. D. et al. Overview of the CCP4 suite and current developments. Acta. Crystallogr. D. Biol. Crystallogr. 67, 235-242 (2011).
27. Vagin, A. & Teplyakov, A. Molecular replacement with MOLREP. Acta. Crystallogr. D. Biol. Crystallogr. 66, 22-25 (2010).
28. Perrakis, A., Morris, R. & Lamzin, V. S. Automated protein model building combined with iterative structure refinement. Nat. Struct. Biol. 6, 458-463 (1999).
29. Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta. Crystallogr. D. Biol. Crystallogr. 66, 213-221 (2010).
30. Konarev, P. V., Petoukhov, M. V., Volkov, V. V. & Svergun, D. I. ATSAS 2.1, a program package for small-angle scattering data analysis. J. Appl. Crystallogr. 39, 277-286 (2006).
31. Svergun, D., Barberato, C. & Koch, M. H. J. CRYSOL-A program to evaluate x-ray solution scattering of biological macromolecules from atomic coordinates. J. Appl. Crystallogr. 28, 768-773 (2009).
32. Franke, D. & Svergun, D. I. DAMMIF, a program for rapid ab-initio shape determination in small-angle scattering. J. Appl. Crystallogr. 42, 342-346 (2009).
33. Svergun, D. I., Petoukhov, M. V. & Koch, M. H. Determination of domain structure of proteins from X-ray solution scattering. Biophys. J. 80, 2946-2953 (2001).
34. Kozin, M. B. & Svergun, D. I. Automated matching of high-and low-resolution structural models. J. Appl. Crystallogr. 36, 860-864 (2001).
35. Volkov, V. V. & Svergun, D. I. Automated matching of high-and low-resolution structural models. J. Appl. Crystallogr. 36, 860-864 (2003).
36. Wriggers, W. & Chacon, P. Using Situs for the registration of protein structures with low-resolution bead models from X-ray solution scattering. J. Appl. Crystallogr. 34, 773-776 (2001).
37. Baykov, A. A., Evtushenko, O. A. & Avaeva, S. M. A malachite green procedure for orthophosphate determination and its use in alkaline phosphatase-based enzyme immunoassay. Anal. Biochem. 171, 266-270 (1988).
38. Pollak, N., Niere, M. & Ziegler, M. NAD kinase levels control the NADPH concentration in human cells. J. Biol. Chem. 282, 33562-33571 (2007).