Mechanistic and structural basis for inhibition of thymidylate synthase ThyX

Open Biology

Volumn 2, Issue OCT, 2012, Pages

  Basta, Tamara ^a   Boum, Yap ^b   Briffotaux, Julien ^a   Becker, Hubert F ^a,c   Lamarre Jouenne, Isabelle ^a   Lambry, Jean Christophe ^a   Skouloubris, Stephane ^a,e   Liebl, Ursula ^a   Graille, Marc ^d,e   Van Tilbeurgh, Herman ^d,e   Myllykallio, Hannu ^a  

^a LABORATOIRE D OPTIQUE ET BIOSCIENCES   (France)

^b EPICENTRE   (France)

^c SORBONNE UNIVERSITÉ   (France)

^d INSTITUTE FOR INTEGRATIVE BIOLOGY OF THE CELL I2BC   (France)

^e UNIVERSITÉ PARIS SACLAY   (France)

Author keywords

Antimicrobial compounds; Inhibitor screen; Naphthoquinone; Thymidylate synthase ThyX

Indexed keywords

ANTIINFECTIVE AGENT; BACTERIAL PROTEIN; NAPHTHOQUINONE; THYMIDYLATE SYNTHASE;

ANTIMICROBIAL COMPOUNDS; ARTICLE; BINDING SITE; CHEMISTRY; CHLAMYDIA TRACHOMATIS; DRUG ANTAGONISM; ENZYMOLOGY; ESCHERICHIA COLI; GENETICS; HELICOBACTER PYLORI; HUMAN; INHIBITOR SCREEN; MYCOBACTERIUM TUBERCULOSIS; PROTEIN TERTIARY STRUCTURE; THYMIDYLATE SYNTHASE THYX; X RAY CRYSTALLOGRAPHY;

ANTIMICROBIAL COMPOUNDS; INHIBITOR SCREEN; NAPHTHOQUINONE; THYMIDYLATE SYNTHASE THYX;

ANTI-INFECTIVE AGENTS; BACTERIAL PROTEINS; BINDING SITES; CHLAMYDIA TRACHOMATIS; CRYSTALLOGRAPHY, X-RAY; ESCHERICHIA COLI; HELICOBACTER PYLORI; HUMANS; MYCOBACTERIUM TUBERCULOSIS; PROTEIN STRUCTURE, TERTIARY; THYMIDYLATE SYNTHASE;

EID: 84877724213     PISSN: None     EISSN: 20462441     Source Type: Journal    
DOI: 10.1098/rsob.120120     Document Type: Article

References (37)

1. Carreras CW, Santi DV. 1995 The catalytic mechanism and structure of thymidylate synthase. Annu. Rev. Biochem. 64, 721-762. (doi:10.1146/annurev.bi. 64.070195.003445)
2. Garg D, Henrich S, Salo-Ahen OM, Myllykallio H, Costi MP, Wade RC. 2010 Novel approaches for targeting thymidylate synthase to overcome the resistance and toxicity of anticancer drugs. J. Med. Chem. 53, 6539-6549. (doi:10.1021/jm901869w)
3. Chernyshev A, Fleischmann T, Kohen A. 2007 Thymidyl biosynthesis enzymes as antibiotic targets. Appl. Microbiol. Biotechnol. 74, 282-289. (doi:10.1007/s00253-006-0763-1)
4. Myllykallio H, Lipowski G, Leduc D, Filee J, Forterre P, Liebl U. 2002 An alternative flavin-dependent mechanism for thymidylate synthesis. Science 297, 105-107. (doi:10.1126/science.1072113)
5. Graziani S et al. 2006 Catalytic mechanism and structure of viral flavin-dependent thymidylate synthase ThyX. J. Biol. Chem. 281, 24048-24057. (doi:10.1074/jbc.M600745200)
6. Mathews II, Deacon AM, Canaves JM, McMullan D, Lesley SA, Agarwalla S, Kuhn P. 2003 Functional analysis of substrate and cofactor complex structures of a thymidylate synthase-complementing protein. Structure 11, 677-690. (doi:10.1016/S0969-2126(03)00097-2)
7. Murzin AG. 2002 DNA building block reinvented. Science 297, 61-62. (doi:10.1126/science.1073910)
8. Sampathkumar P, Turley S, Ulmer JE, Rhie HG, Sibley CH, Hol WGJ. 2005 Structure of the Mycobacterium tuberculosis flavin dependent thymidylate synthase (MtbThyX) at 2.0 Å resolution. J. Mol. Biol. 352, 1091-1104. (doi:10.1016/j.jmb.2005.07.071)
9. Koehn EM, Fleischmann T, Conrad JA, Palfey BA, Lesley SA, Mathews II, Kohen A. 2009 An unusual mechanism of thymidylate biosynthesis in organisms containing the ThyX gene. Nature 458, 919-923. (doi:10.1038/nature07973)
10. Mishanina TV, Koehn EM, Conrad JA, Palfey BA, Lesley SA, Kohen A. 2012 Trapping of an intermediate in the reaction catalyzed by flavin-dependent thymidylate synthase. J. Am. Chem. Soc. 134, 4442-4448. (doi:10.1021/ja2120822)
11. Mishanina TV, Koehn EM, Kohen A. 2011 Mechanisms and inhibition of uracil methylating enzymes. Bioorg. Chem. 43, 37-43. (doi:10.1016/j.bioorg.2011.11. 005)
12. Kallen RG, Simon M, Marmur J. 1962 The new occurrence of a new pyrimidine base replacing thymine in a bacteriophage DNA:5-hydroxymethyl uracil. J. Mol. Biol. 5, 248-250. (doi:10.1016/S0022-2836(62)80087-4)
13. Wilhelm K, Ruger W. 1992 Deoxyuridylate-hydroxymethylase of bacteriophage SPO1. Virology 189, 640-646. (doi:10.1016/0042-6822(92)90587-F)
14. Forterre P, Filée J, Myllykallio H. 2000 Origin and evolution of DNA and DNA replication machineries. Austin, TX: Landes Bioscience.
15. Leduc D, Graziani S, Lipowski G, Marchand C, Le Marechal P, Liebl U, Myllykallio H. 2004 Functional evidence for active site location of tetrameric thymidylate synthase X at the interphase of three monomers. Proc. Natl Acad. Sci. USA 101, 7252-7257. (doi:10.1073/pnas.0401365101)
16. Giladi M, Bitan-Banin G, Mevarech M, Ortenberg R. 2002 Genetic evidence for a novel thymidylate synthase in the halophilic archaeon Halobacterium salinarum and in Campylobacter jejuni. FEMS Microbiol. Lett. 216, 105-109. (doi:10.1111/j.1574-6968.2002.tb11422.x)
17. Graziani S, Xia Y, Gurnon JR, Van Etten JL, Leduc D, Skouloubris S, Myllykallio H, Liebl U. 2004 Functional analysis of FAD-dependent thymidylate synthase ThyX from Paramecium bursaria chlorella virus-1. J. Biol. Chem. 279, 54340-54347. (doi:10.1074/jbc.M409121200)
18. Koehn EM, Perissinotti LL, Moghram S, Prabhakar A, Lesley SA et al. In press. The folate binding site of flavin-dependent thymidylate synthase. Proc. Natl Acad. Sci. USA. (doi:10.1073/pnas.1206077109)
19. Ulmer JE, Boum Y, Thouvenel CD, Myllykallio H, Sibley CH. 2008 Functional analysis of the Mycobacterium tuberculosis FAD-dependent thymidylate synthase, ThyX, reveals new amino acid residues contributing to an extended ThyX motif. J. Bacteriol. 190, 2056-2064. (doi:10.1128/JB.01094-07)
20. Kogler M, Busson R, De Jonghe S., Rozenski J, Van Belle K., Louat T, Munier-Lehmann H, Herdewijn P. 2012 Synthesis and evaluation of 6-aza-2'-deoxyuridine monophosphate analogs as inhibitors of thymidylate synthases, and as substrates or inhibitors of thymidine monophosphate kinase in Mycobacterium tuberculosis. Chem. Biodivers. 9, 536-556. (doi:10.1002/cbdv. 201100285)
21. Esra Onen F, Boum Y, Jacquement C, Spanedda MV, Jaber N, Scherman D, Myllykallio H, Herscovici J. 2008 Design, synthesis and evaluation of potent thymidylate synthase X inhibitors. Bioorg. Med. Chem. Lett. 18, 3628-3631. (doi:10.1016/j.bmcl.2008.04.080)
22. Kogler M et al. 2011 Synthesis and evaluation of 5-substituted 2'-deoxyuridine monophosphate analogues as inhibitors of flavin-dependent thymidylate synthase in Mycobacterium tuberculosis. J. Med. Chem. 54, 4847-4862. (doi:10.1021/jm2004688)
23. Leduc D, Escartin F, Nijhout HF, Reed MC, Liebl U, Skouloubris S, Myllykallio H. 2007 Flavin-dependent thymidylate synthase ThyX activity: implications for the folate cycle in bacteria. J. Bacteriol. 189, 8537-8545. (doi:10.1128/JB.01380-07)
24. 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. (doi:10.1099/mic.0.053983-0)
25. Park M, Cho S, Lee H, Sibley CH, Rhie H. 2010 Alternative thymidylate synthase, ThyX, involved in Corynebacterium glutamicum ATCC 13032 survival during stationary growth phase. FEMS Microbiol. Lett. 307, 128-134. (doi:10.1111/j.1574-6968.2010.01971.x)
26. Chernyshev A, Fleischmann T, Koehn EM, Lesley SA, Kohen A. 2007 The relationships between oxidase and synthase activities of flavin dependent thymidylate synthase (FDTS). Chem. Commun. (Camb) 2007, 2861-2863. (doi:10.1039/b700977a)
27. Trott O, Olson AJ. 2010 AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 31, 455-461. (doi:10.1002/jcc.21334)
28. Wang Z, Chernyshev A, Koehn EM, Manuel TD, Lesley SA, Kohen A. 2009 Oxidase activity of a flavin-dependent thymidylate synthase. FEBS J. 276, 2801-2810. (doi:10.1111/j.1742-4658.2009.07003.x)
29. Copeland RA. 2005 Evaluation of enzyme inhibitors in drug discovery, pp. 48-81. Hoboken, NJ: John Wiley & Sons, Inc.
30. Escartin F, Skouloubris S, Liebl U, Myllykallio H. 2008 Flavin-dependent thymidylate synthase X limits chromosomal DNA replication. Proc. Natl Acad. Sci. USA 105, 9948-9952. (doi:10.1073/pnas.0801356105)
31. Faig M, Bianchet MA, Talalay P, Chen S, Winski S, Ross D, Amzel LM. 2000 Structures of recombinant human and mouse NAD(P)H: quinone oxidoreductases: species comparison and structural changes with substrate binding and release. Proc. Natl Acad. Sci. USA 97, 3177-3182. (doi:10.1073/pnas.97.7.3177)
32. Li R, Bianchet MA, Talalay P, Amzel LM. 1995 The three-dimensional structure of NAD(P)H: quinone reductase, a flavoprotein involved in cancer chemoprotection and chemotherapy: mechanism of the two-electron reduction. Proc. Natl Acad. Sci. USA 92, 8846-8850. (doi:10.1073/pnas.92.19.8846)
33. Barton V, Fisher N, Biagini GA, Ward SA, O'Neill PM. 2010 Inhibiting Plasmodium cytochrome bc1: a complex issue. Curr. Opin. Chem. Biol. 14, 440-446. (doi:10.1016/j.cbpa.2010.05.005)
34. Hansen M, Le Nours J, Johansson E, Antal T, Ullrich A, Löffler M, Larsen S. 2004 Inhibitor binding in a class 2 dihydroorotate dehydrogenase causes variations in the membrane-associated N-terminal domain. Protein Sci. 13, 1031-1042. (doi:10.1110/ps.03533004)
35. Williams JW, Morrison JF, Duggleby RG. 1979 Methotrexate, a high-affinity pseudosubstrate of dihydrofolate reductase. Biochemistry 18, 2567-2573. (doi:10.1021/bi00579a021)
36. Murakami K, Haneda M, Iwata S, Yoshino M. 2012 Effect of hydroxy substituent on the prooxidant action of naphthoquinone compounds. Toxicol. In Vitro 24, 905-909. (doi:10.1016/j.tiv.2009.11.018)
37. Ollinger K, Brunmark A. 1991 Effect of hydroxy substituent position on 1,4-naphthoquinone toxicity to rat hepatocytes. J. Biol. Chem. 266, 21496-21503.