Thymidyl biosynthesis enzymes as antibiotic targets

Applied Microbiology and Biotechnology

Volumn 74, Issue 2, 2007, Pages 282-289

  Chernyshev, Anatoly ^a   Fleischmann, Todd ^a   Kohen, Amnon ^a  

^a The University of Iowa   (United States)

Author keywords

Biosynthesis; Flavin; Thymidylate Synthase; Thymine

Indexed keywords

FLAVIN; THYMIDYLATE SYNTHASE; THYMINE;

ANTIBIOTICS; BIOSYNTHESIS; ENZYME KINETICS; GENETIC ENGINEERING; PATHOLOGY;

ENZYMES;

ANTIBIOTIC AGENT; FLUOROURACIL; ISOENZYME; METHOTREXATE; METHYL GROUP; METHYLENETETRAHYDROFOLIC ACID; QUERCETIN; RIBOTHYMIDYL SYNTHASE; THYMIDYLATE SYNTHASE; UNCLASSIFIED DRUG;

ANTIBIOTICS; DISEASE CONTROL; DRUG DEVELOPMENT; ENZYME ACTIVITY; METHYLATION; ORGANIC NITROGEN COMPOUND;

BACILLUS ANTHRACIS; DRUG TARGETING; ENZYME ACTIVITY; ISOENZYME ANALYSIS; METHYLATION; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; SALMONELLA TYPHI; SHORT SURVEY; STRUCTURAL HOMOLOGY;

ANTI-BACTERIAL AGENTS; DRUG DESIGN; ENZYME INHIBITORS; FLAVINS; FOLIC ACID; HUMANS; METHYLTRANSFERASES; THYMIDINE; THYMIDYLATE SYNTHASE;

EID: 33846845204     PISSN: 01757598     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00253-006-0763-1     Document Type: Short Survey

References (44)

1. Agrawal N, Lesley SA, Kuhn P, Kohen A (2004) Mechanistic studies of a flavin-dependent thymidylate synthase. Biochemistry 43:10295-10301
2. Atreya CE, Anderson KS (2004) Kinetic characterization of bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) from Cryptosporidium hominis: a paradigm shift for ts activity and channeling behavior. J Biol Chem 279:18314-18322
3. Atreya CE, Johnson EF, Irwin JJ, Dow A, Massimine KM, Coppens I, Stempliuk V, Beverley S, Joiner KA, Shoichet BK, Anderson KS (2003) A molecular docking strategy identifies Eosin B as a non-active site inhibitor of protozoal bifunctional thymidylate synthase-dihydrofolate reductase. J Biol Chem 278:14092-14100
4. Barrett JE, Maltby DA, Santi DV, Schultz PG (1998) Trapping of the C5 methylene intermediate in thymidylate synthase. J Am Chem Soc 120:449-450
5. Carreras CW, Santi DV (1995) The catalytic mechanism and structure of thymidylate synthase. Annu Rev Biochem 64:721-762
6. Chu E, Voeller D, Koeller DM, Drake JC, Takimoto CH, Maley GF, Maley F, Allegra CJ (1993) Identification of an RNA binding site for human thymidylate synthase. Proc Natl Acad Sci USA 90:517-521
7. Danenberg PV, Malli H, Swenson S (1999) Thymidylate synthase inhibitors. Semin Oncol 26:621-631
8. Delk AS, Rabinowitz JC (1975) Biosynthesis of ribosylthymine in the transfer RNA of Streptococcus faecalis: a folate-dependent methylation not involving S-adenosylmethionine. Proc Natl Acad Sci USA 72:528-530
9. Delk AS, Romeo JM, Nagle DP Jr, Rabinowitz JC (1976) Biosynthesis of ribothymidine in the transfer RNA of Streptococcus faecalis and Bacillus subtilis. A methylation of RNA involving 5,10- methylenetetrahydrofolate. J Biol Chem 251:7649-7656
10. Delk AS, Nagle DP Jr, Rabinowitz JC, Straub KM (1979) The methylenetetrahydrofolate-mediated biosynthesis of ribothymidine in the transfer-RNA of Streptococcus faecalis: incorporation of hydrogen from solvent into the methyl moiety. Biochem Biophys Res Commun 86:244-251
11. Delk AS, Nagle DP Jr, Rabinowitz JC (1980) Methylenetetrahydrofolate- dependent biosynthesis of ribothymidine in transfer RNA of Streptococcus faecalis. Evidence for reduction of the 1-carbon unit by FADH2. J Biol Chem 255:4387-4390
12. Gattis SG, Palfey BA (2005) Direct observation of the participation of flavin in product formation by thyX-encoded thymidylate synthase. J Am Chem Soc 127:832-833
13. Graziani S et al. (2004) Functional analysis of FAD-dependent thymidylate synthase ThyX from paramecium bursaria chlorella virus-1. J Biol Chem 279:54340-54347
14. Graziani S, Bernauer J, Skouloubris S, Graille M, Zhou CZ, Marchand C, Decottignies P, van Tilbeurgh H, Myllykallio H, Liebl U (2006) Catalytic mechanism and structure of viral flavindependent thymidylate synthase ThyX. J Biol Chem 281 (33):24048-24057
15. Griffin J, Roshick C, Iliffe-Lee E, McClarty G (2005) Catalytic mechanism of Chlamydia trachomatis flavin-dependent thymidylate synthase. J Biol Chem 280:5456-5467
16. Ivanetich KM, Santi DV (1990) Bifunctional thymidylate synthase-dihydrofolate reductase in protozoa. Faseb J 4:1591-1597
17. Johnson EF, Hinz W, Atreya CE, Maley F, Anderson KS (2002) Mechanistic characterization of Toxoplasma gondii thymidylate synthase (TS-DHFR)-dihydrofolate reductase. Evidence for a TS intermediate and TS half-sites reactivity. J Biol Chem 277:43126-43136
18. Kanai F, Sawa T, Hamada M, Naganawa H, Takeuchi T, Umezawa H (1983) Vanoxonin, a new inhibitor of thymidylate synthetase. J Antibiot (Tokyo) 36:656-660
19. Kanai F, Isshiki K, Umezawa Y, Morishima H, Naganawa H, Takita T, Takeuchi T, Umezawa H (1985a) Vanoxonin, a new inhibitor of thymidylate synthetase. II. Structure determination and total synthesis. J Antibiot (Tokyo) 38:31-38
20. Kanai F, Kaneko T, Morishima H, Isshiki K, Takita T, Takeuchi T, Umezawa H (1985b) Vanoxonin, a new inhibitor of thymidylate synthetase. III. Inhibition of thymidylate synthetase by vanoxonin-vanadium complex. J Antibiot (Tokyo) 38:39-50
21. Kanai A, Sato A, Imoto J, Tomita M (2006) Archaeal Pyrococcus furiosus thymidylate synthase 1 is an RNA-binding protein. Biochem J 393:373-379
22. Kealey JT, Santi DV (1995) Stereochemistry of tRNA(m5U54)- methyltransferase catalysis: 19F NMR spectroscopy of an enzyme-FUraRNA covalent complex. Biochemistry 34:2441-2446 Kealey JT, Gu X, Santi DV (1994) Enzymatic mechanism of tRNA (m5U54)methyltransferase. Biochimie 76:1133-1142
23. Kuhn P, Lesley SA, Mathews II, Canaves JM, Brinen LS, Dai X, Deacon AM, Elsliger MA, Eshaghi S, Floyd R, Godzik A, Grittini C, Grzechnik SK, Guda C, Hodgson KO, Jaroszewski L, Karlak C, Klock HE, Koesema E, Kovarik JM, Kreusch AT, McMullan D, McPhillips TM, Miller MA, Miller M, Morse A, Mon K, Ouyang J, Robb A, Rodrigues K, Selby TL, Spraggon G, Stevens RC, Taylor SS, Van den Bedem H, Velasquez J, Vincent J, Wang X, West B, Wolf G, Wooley J, Wilson IA (2002) Crystal structure of thy1, a thymidylate synthase complementing protein from thermotoga maritima at 2.25 Å resolution. Protein Struc Funct Genet 49:142-145
24. Leduc D, Graziani S, Lipowski G, Marchand C, Le Maréchal P, Liebl U, Myllykallio H (2004a) 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
25. Leduc D, Graziani S, Meslet-Cladiere L, Sodolescu A, Liebl U, Myllykallio H (2004b) Two distinct pathways for thymidylate (dTMP) synthesis in (hyper)thermophilic Bacteria and Archaea. Biochem Soc Trans 32:231-235
26. Lee TT, Agarwalla S, Stroud RM (2004) Crystal structure of RumA, an iron-sulfur cluster containing E. coli ribosomal RNA 5-methyluridine methyltransferase. Structure 12:397-407
27. Lee TT, Agarwalla S, Stroud RM (2005) A unique RNA Fold in the RumA-RNA-cofactor ternary complex contributes to substrate selectivity and enzymatic function. Cell 120:599-611
28. Lesley SA, Kuhn P, Godzik A, Deacon AM, Mathews I, Kreusch A, Spraggon G, Klock HE, McMullan D, Shin T, Vincent J, Robb A, Brinen LS, Miller MD, McPhillips TM, Miller MA, Scheibe D, Canaves JM, Guda C, Jaroszewski L, Selby TL, Elsliger M-A, Wooley J, Taylor SS, Hodgson KO,Wilson IA, Schultz PG, Stevens RC (2002) Structural genomics of the Thermotoga maritima proteome implemented in a high-throughput structure determination pipeline. Proc Natl Acad Sci USA 99:11664-11669
29. Liu J, Schmitz JC, Lin X, Tai N, Yan W, Farrell M, Bailly M, Chen T, Chu E (2002) Thymidylate synthase as a translational regulator of cellular gene expression. Biochim Biophys Acta 1587:174-182
30. Mason A, Agrawal N, Washington MT, Lesley SA, Kohen A (2006) A lag-phase in the reduction of flavin dependent thymidylate synthase (FDTS) revealed a mechanistic missing link. Chem Commun 16:1781-1783
31. 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
32. Mattevi A (2006) To be or not to be an oxidase: challenging the oxygen reactivity of flavoenzymes. Trends Biochem Sci 31:276-283
33. Murzin AG (2002) Biochemistry. DNA building block reinvented. Science 297:61-62
34. Myllykallio H, Lipowski G, Leduc D, Filee J, Forterre P, Liebl U (2002) An alternative flavin-dependent mechanism of thymidylate synthesis. Science 297:105-107
35. Persson BC, Grustafsson C, Berg DE, Bjork GR (1992) The gene for a tRNA modifying enzyme, m5U54-methyltransferase, is essential for viability in Escherichia coli. Proc Natl Acad Sci USA 89:3995-3998
36. Pharkya P, Nikolaev EV, Maranas CD (2003) Review of the BRENDA Database. Metab Eng 5:71-73
37. Romeo JM, Delk AS, Rabinowitz JC (1974) The occurrence of a transmethylation reaction not involving S-adenosylmethionine in the formation of ribothymidine in Bacillus subtilis transfer-RNA. Biochem Biophys Res Commun 61:1256-1261
38. 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 resolution. J Mol Biol 352:1091-1104
39. 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
40. Shoichet BK, Stroud RM, Santi DV, Kuntz ID, Perry KM (1993) Structure-based discovery of inhibitors of thymidylate synthase. Science 259:1445-1450
41. Stout TJ, Tondi D, Rinaldi M, Barlocco D, Pecorari P, Santi DV, Kuntz ID, Stroud RM, Shoichet BK, Costi MP (1999) Structure-based design of inhibitors specific for bacterial thymidylate synthase. Biochemistry 38:1607-1617
42. Tai N, Schmitz JC, Liu J, Lin X, Bailly M, Chen TM, Chu E (2004) Translational autoregulation of thymidylate synthase and dihydrofolate reductase. Front Biosci 9:2521-2526
43. Tondi D, Slomczynska U, Costi MP, Watterson DM, Ghelli S, Shoichet BK (1999) Structure-based discovery and in-parallel optimization of novel competitive inhibitors of thymidylate synthase. Chem Biol 6:319-331
44. Urbonavicius J, Skouloubris S, Myllykallio H, Grosjean H (2005) Identification of a novel gene encoding a flavin-dependent tRNA: m5U methyltransferase in bacteria-evolutionary implications. Nucleic Acids Res 33:3955-3964