The dutpase enzyme is essential in Mycobacterium smegmatis

PLoS ONE

Volumn 7, Issue 5, 2012, Pages

  Pecsi, Ildiko ^a,b   Hirmondo, Rita ^a   Brown, Amanda C ^b   Lopata, Anna ^a   Parish, Tanya ^b   Vertessy, Beata G ^a,c   Tóth, Judit ^a  

^a INSTITUTE OF EXPERIMENTAL MEDICINE   (Hungary)

^b QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^c BUDAPEST UNIVERSITY OF TECHNOLOGY AND ECONOMICS   (Hungary)

Author keywords

[No Author keywords available]

Indexed keywords

DEOXYURIDINE TRIPHOSPHATE PYROPHOSPHATASE; DUTP PYROPHOSPHATASE; INORGANIC PYROPHOSPHATASE;

ARTICLE; BACTERIAL CELL; CONTROLLED STUDY; ENZYME ACTIVITY; GENE INACTIVATION; GENE STRUCTURE; GENETIC COMPLEMENTATION; IN VITRO STUDY; MUTANT; MYCOBACTERIUM SMEGMATIS; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; STRUCTURE ACTIVITY RELATION; WILD TYPE; AMINO ACID SEQUENCE; ATYPICAL MYCOBACTERIOSIS; CHEMISTRY; ENZYMOLOGY; GENETICS; GENOMICS; GROWTH, DEVELOPMENT AND AGING; HUMAN; METABOLISM; MOLECULAR GENETICS; MUTATION; SEQUENCE ALIGNMENT; VIROLOGY;

BACTERIA (MICROORGANISMS); CORYNEBACTERINEAE; MYCOBACTERIUM SMEGMATIS; MYCOBACTERIUM TUBERCULOSIS;

AMINO ACID SEQUENCE; GENE KNOCKOUT TECHNIQUES; GENOMICS; HUMANS; MOLECULAR SEQUENCE DATA; MUTATION; MYCOBACTERIUM INFECTIONS, NONTUBERCULOUS; MYCOBACTERIUM SMEGMATIS; MYCOBACTERIUM TUBERCULOSIS; PYROPHOSPHATASES; SEQUENCE ALIGNMENT;

EID: 84861438630     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0037461     Document Type: Article

References (61)

1. Furlow B, (2010) Tuberculosis: a review and update. Radiol Technol 82: 33-52.
2. Jagielski T, Augustynowa-Kopec E, Zwolska Z, (2010) Epidemiology of tuberculosis: a global, European and Polish perspective. Wiad Lek 63: 230-246.
3. WHO, (2010) Global Tuberculosis Control: World Health Organization.
4. Chakroborty A Drug-resistant tuberculosis: an insurmountable epidemic? Inflammopharmacology.
5. Jassal M, Bishai WR, (2009) Extensively drug-resistant tuberculosis. Lancet Infect Dis 9: 19-30.
6. Harries AD, Dye C, (2006) Tuberculosis. Ann Trop Med Parasitol 100: 415-431.
7. Koul A, Arnoult E, Lounis N, Guillemont J, Andries K, (2011) The challenge of new drug discovery for tuberculosis. Nature 469: 483-490.
8. Chernyshev A, Fleischmann T, Kohen A, (2007) Thymidyl biosynthesis enzymes as antibiotic targets. Appl Microbiol Biotechnol 74: 282-289.
9. Vertessy BG, Toth J, (2009) Keeping uracil out of DNA: physiological role, structure and catalytic mechanism of dUTPases. Acc Chem Res 42: 97-106.
10. Varga B, Barabas O, Takacs E, Nagy N, Nagy P, et al. (2008) Active site of mycobacterial dUTPase: structural characteristics and a built-in sensor. Biochem Biophys Res Commun 373: 8-13.
11. Takacs E, Nagy G, Leveles I, Harmat V, Lopata A, et al. (2010) Direct contacts between conserved motifs of different subunits provide major contribution to active site organization in human and mycobacterial dUTPases. FEBS Lett 584: 3047-3054.
12. Chan S, Segelke B, Lekin T, Krupka H, Cho US, et al. (2004) Crystal structure of the Mycobacterium tuberculosis dUTPase: insights into the catalytic mechanism. J Mol Biol 341: 503-517.
13. Ladner RD, (2001) The role of dUTPase and uracil-DNA repair in cancer chemotherapy. Curr Protein Pept Sci 2: 361-370.
14. Whittingham JL, Leal I, Nguyen C, Kasinathan G, Bell E, et al. (2005) dUTPase as a platform for antimalarial drug design: structural basis for the selectivity of a class of nucleoside inhibitors. Structure 13: 329-338.
15. Wilson PM, Fazzone W, LaBonte MJ, Lenz HJ, Ladner RD, (2009) Regulation of human dUTPase gene expression and p53-mediated transcriptional repression in response to oxaliplatin-induced DNA damage. Nucleic Acids Res 37: 78-95.
16. Wilson PM, Fazzone W, LaBonte MJ, Deng J, Neamati N, et al. (2008) Novel opportunities for thymidylate metabolism as a therapeutic target. Mol Cancer Ther 7: 3029-3037.
17. Nyman PO, (2001) Introduction. dUTPases. Curr Protein Pept Sci 2: 277-285.
18. Mustafi D, Bekesi A, Vertessy BG, Makinen MW, (2003) Catalytic and structural role of the metal ion in dUTP pyrophosphatase. Proc Natl Acad Sci U S A 100: 5670-5675.
19. Fiser A, Vertessy BG, (2000) Altered subunit communication in subfamilies of trimeric dUTPases. Biochem Biophys Res Commun 279: 534-542.
20. Kovari J, Barabas O, Takacs E, Bekesi A, Dubrovay Z, et al. (2004) Altered active site flexibility and a structural metal-binding site in eukaryotic dUTPase: kinetic characterization, folding, and crystallographic studies of the homotrimeric Drosophila enzyme. J Biol Chem 279: 17932-17944.
21. Horvath A, Vertessy BG, (2010) A one-step method for quantitative determination of uracil in DNA by real-time PCR. Nucleic Acids Res 38: e196.
22. Lari SU, Chen CY, Vertessy BG, Morre J, Bennett SE, (2006) Quantitative determination of uracil residues in Escherichia coli DNA: Contribution of ung, dug, and dut genes to uracil avoidance. DNA Repair (Amst) 5: 1407-1420.
23. Merenyi G, Kovari J, Toth J, Takacs E, Zagyva I, et al. (2011) Cellular response to efficient dUTPase RNAi silencing in stable HeLa cell lines perturbs expression levels of genes involved in thymidylate metabolism. Nucleosides Nucleotides Nucleic Acids 30: 369-390.
24. Huffman JL, Li H, White RH, Tainer JA, (2003) Structural basis for recognition and catalysis by the bifunctional dCTP deaminase and dUTPase from Methanococcus jannaschii. J Mol Biol 331: 885-896.
25. Johansson E, Bjornberg O, Nyman PO, Larsen S, (2003) Structure of the bifunctional dCTP deaminase-dUTPase from Methanocaldococcus jannaschii and its relation to other homotrimeric dUTPases. J Biol Chem 278: 27916-27922.
26. Helt SS, Thymark M, Harris P, Aagaard C, Dietrich J, et al. (2008) Mechanism of dTTP inhibition of the bifunctional dCTP deaminase: dUTPase encoded by Mycobacterium tuberculosis. J Mol Biol 376: 554-569.
27. Bjornberg O, Neuhard J, Nyman PO, (2003) A bifunctional dCTP deaminase-dUTP nucleotidohydrolase from the hyperthermophilic archaeon Methanocaldococcus jannaschii. J Biol Chem 278: 20667-20672.
28. el-Hajj HH, Zhang H, Weiss B, (1988) Lethality of a dut (deoxyuridine triphosphatase) mutation in Escherichia coli. J Bacteriol 170: 1069-1075.
29. Gadsden MH, McIntosh EM, Game JC, Wilson PJ, Haynes RH, (1993) dUTP pyrophosphatase is an essential enzyme in Saccharomyces cerevisiae. EMBO J 12: 4425-4431.
30. Guillet M, Van Der Kemp PA, Boiteux S, (2006) dUTPase activity is critical to maintain genetic stability in Saccharomyces cerevisiae. Nucleic Acids Res 34: 2056-2066.
31. Sassetti CM, Boyd DH, Rubin EJ, (2003) Genes required for mycobacterial growth defined by high density mutagenesis. Mol Microbiol 48: 77-84.
32. Griffin JE, Gawronski JD, Dejesus MA, Ioerger TR, Akerley BJ, et al. (2011) High-resolution phenotypic profiling defines genes essential for mycobacterial growth and cholesterol catabolism. PLoS Pathog 7: e1002251.
33. Pecsi I, Leveles I, Harmat V, Vertessy BG, Toth J, (2010) Aromatic stacking between nucleobase and enzyme promotes phosphate ester hydrolysis in dUTPase. Nucleic Acids Res 38: 7179-7186.
34. Barabas O, Pongracz V, Kovari J, Wilmanns M, Vertessy BG, (2004) Structural insights into the catalytic mechanism of phosphate ester hydrolysis by dUTPase. J Biol Chem 279: 42907-42915.
35. Johansson E, Fano M, Bynck JH, Neuhard J, Larsen S, et al. (2005) Structures of dCTP deaminase from Escherichia coli with bound substrate and product: reaction mechanism and determinants of mono- and bifunctionality for a family of enzymes. J Biol Chem 280: 3051-3059.
36. Parish T, Stoker NG, (2000) Use of a flexible cassette method to generate a double unmarked Mycobacterium tuberculosis tlyA plcABC mutant by gene replacement. Microbiology 146 (Pt 8): 1969-1975.
37. Toth J, Varga B, Kovacs M, Malnasi-Csizmadia A, Vertessy BG, (2007) Kinetic mechanism of human dUTPase, an essential nucleotide pyrophosphatase enzyme. J Biol Chem 282: 33572-33582.
38. Dos Vultos T, Mestre O, Tonjum T, Gicquel B, (2009) DNA repair in Mycobacterium tuberculosis revisited. FEMS Microbiol Rev 33: 471-487.
39. Springer B, Sander P, Sedlacek L, Hardt WD, Mizrahi V, et al. (2004) Lack of mismatch correction facilitates genome evolution in mycobacteria. Mol Microbiol 53: 1601-1609.
40. Boshoff HI, Reed MB, Barry CE 3rd, Mizrahi V, (2003) DnaE2 polymerase contributes to in vivo survival and the emergence of drug resistance in Mycobacterium tuberculosis. Cell 113: 183-193.
41. Varga B, Barabas O, Kovari J, Toth J, Hunyadi-Gulyas E, et al. (2007) Active site closure facilitates juxtaposition of reactant atoms for initiation of catalysis by human dUTPase. FEBS Lett 581: 4783-4788.
42. Pecsi I, Szabo JE, Adams SD, Simon I, Sellers JR, et al. (2011) Nucleotide pyrophosphatase employs a P-loop-like motif to enhance catalytic power and NDP/NTP discrimination. Proc Natl Acad Sci U S A 108: 14437-14442.
43. Raghunand TR, Bishai WR, (2006) Mapping essential domains of Mycobacterium smegmatis WhmD: insights into WhiB structure and function. J Bacteriol 188: 6966-6976.
44. Sinha KM, Glickman MS, Shuman S, (2009) Mutational analysis of Mycobacterium UvrD1 identifies functional groups required for ATP hydrolysis, DNA unwinding, and chemomechanical coupling. Biochemistry 48: 4019-4030.
45. Tormo-Mas MA, Mir I, Shrestha A, Tallent SM, Campoy S, et al. (2010) Moonlighting bacteriophage proteins derepress staphylococcal pathogenicity islands. Nature 465: 779-782.
46. Sassetti CM, Rubin EJ, (2003) Genetic requirements for mycobacterial survival during infection. Proc Natl Acad Sci U S A 100: 12989-12994.
47. Sampathkumar P, Turley S, Sibley CH, Hol WG, (2006) NADP+ expels both the co-factor and a substrate analog from the Mycobacterium tuberculosis ThyX active site: opportunities for anti-bacterial drug design. J Mol Biol 360: 1-6.
48. Fivian-Hughes AS, Houghton J, Davis EO, (2012) Mycobacterium tuberculosis thymidylate synthase gene thyX is essential and potentially bifunctional, while thyA deletion confers resistance to p-aminosalicylic acid. Microbiology 158: 308-318.
49. Jarmula A, (2010) Antifolate inhibitors of thymidylate synthase as anticancer drugs. Mini Rev Med Chem 10: 1211-1222.
50. Cosma CL, Sherman DR, Ramakrishnan L, (2003) The secret lives of the pathogenic mycobacteria. Annu Rev Microbiol 57: 641-676.
51. Mustafa AS, Cockle PJ, Shaban F, Hewinson RG, Vordermeier HM, (2002) Immunogenicity of Mycobacterium tuberculosis RD1 region gene products in infected cattle. Clin Exp Immunol 130: 37-42.
52. Arnold K, Bordoli L, Kopp J, Schwede T, (2006) The SWISS-MODEL workspace: a web-based environment for protein structure homology modelling. Bioinformatics 22: 195-201.
53. Melo F, Feytmans E, (1998) Assessing protein structures with a non-local atomic interaction energy. J Mol Biol 277: 1141-1152.
54. Benkert P, Biasini M, Schwede T, (2011) Toward the estimation of the absolute quality of individual protein structure models. Bioinformatics 27: 343-350.
55. Laskowski R A MMW, Moss D, Thornton J M, (1993) PROCHECK: a program to check the stereochemical quality of protein structures. J Appl Cryst 26, 283-291.
56. Snapper SB, Melton RE, Mustafa S, Kieser T, Jacobs WR Jr, (1990) Isolation and characterization of efficient plasmid transformation mutants of Mycobacterium smegmatis. Mol Microbiol 4: 1911-1919.
57. Roberts G, Muttucumaru DG, Parish T, (2003) Control of the acetamidase gene of Mycobacterium smegmatis by multiple regulators. FEMS Microbiol Lett 221: 131-136.
58. Mahenthiralingam E, Marklund BI, Brooks LA, Smith DA, Bancroft GJ, et al. (1998) Site-directed mutagenesis of the 19-kilodalton lipoprotein antigen reveals No essential role for the protein in the growth and virulence of Mycobacterium intracellulare. Infect Immun 66: 3626-3634.
59. Parish T, Stoker NG, (1998) Electroporation of mycobacteria. Methods Mol Biol 101: 129-144.
60. Goude R, Parish T, (2008) Electroporation of mycobacteria. J Vis Exp.
61. TJ Silhavy, Berman, L M, Enquist, W L, (1984) Experiments with gene fusions; Laboratory. CSH, editor Cold Spring Harbor, N.Y.