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Evolution of vitamin B2 biosynthesis: riboflavin synthase of Arabidopsis thaliana and its inhibition by riboflavin

  • Markus Fischer , Ilka Haase , Richard Feicht , Nicholas Schramek , Peter Köhler , Peter Schieberle and Adelbert Bacher
Published/Copyright: July 5, 2005
Biological Chemistry
From the journal Volume 386 Issue 5

Abstract

A synthetic gene specifying the catalytic domain of the Arabidopsis thaliana riboflavin synthase was expressed with high efficiency in a recombinant Escherichia coli strain. The recombinant pseudomature protein was shown to convert 6,7-dimethyl-8-ribityllumazine into riboflavin at a rate of 0.027 s−1 at 25°C. The protein sediments at a rate of 3.9 S. Sedimentation equilibrium analysis afforded a molecular mass of 67.5 kDa, indicating a homotrimeric structure, analogous to the riboflavin synthases of Eubacteria and fungi. The protein binds its product riboflavin with relatively high affinity (Kd=1.1 μM). Product inhibition results in a characteristic sigmoidal velocity versus substrate concentration relationship. Characterization of the enzyme/product complex by circular dichroism and UV absorbance spectroscopy revealed a shift of the absorption maxima of riboflavin from 370 and 445 to 399 and 465 nm, respectively. Complete or partial sequences for riboflavin synthase orthologs were analyzed from 11 plant species. In each case for which the complete plant gene sequence was available, the catalytic domain was preceded by a sequence of 1–72 amino acid residues believed to function as plastid targeting signals. Comparison of all available riboflavin synthase sequences indicates that hypothetical gene duplication conducive to the two-domain architecture occurred very early in evolution.

Keywords: analytical ultracentrifugation; circular dichroism spectroscopy; kinetic analysis; phylogenetic analysis; plant; synthetic gene
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References

Ahmad, M. and Cashmore, A.R. (1997). The blue-light receptor cryptochrome 1 shows functional dependence on phytochrome A or phytochrome B in Arabidopsis thaliana. Plant J.11, 421–427.10.1046/j.1365-313X.1997.11030421.xSearch in Google Scholar

Altschul, S.F. and Koonin, E.V. (1998). Iterated profile searches with PSI-BLAST – a tool for discovery in protein databases. Trends Biochem. Sci.23, 444–447.10.1016/S0968-0004(98)01298-5Search in Google Scholar

Bacher, A. and Eberhardt, S. (2001). Cloning and characterization of riboflavin synthase from Arabidopsis thaliana and screening for riboflavin synthase-inhibiting herbicides. PCT International Patent Application WO 0134813, 45 pp.Search in Google Scholar

Bacher, A., Schnepple, H., Mailaender, B., Otto, M.K., and Ben-Shaul, Y. (1980). Structure and function of the riboflavin synthase complex of Bacillus subtilis. In: Flavins and Flavoproteins, Proceedings of the 6th International Symposium. pp. 579–586.Search in Google Scholar

Bacher, A., Eberhardt, S., and Richter, G. (1996). Biosynthesis of riboflavin. In: Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology, 2nd Ed., Vol. 1. F.C. Neidhardt, J.L. Ingraham, K.B. Low, B. Magasanik, M. Schaechter, and H.E. Umbarger, eds. (Washington, DC, USA: ASM), pp. 657–664.Search in Google Scholar

Bacher, A., Eberhardt, S., Fischer, M., Mörtl, S., Kis, K., Kugelbrey, K., Scheuring, J., and Schott, K. (1997). Biosynthesis of riboflavin: lumazine synthase and riboflavin synthase. Methods Enzymol.280, 389–399.10.1016/S0076-6879(97)80130-9Search in Google Scholar

Bacher, A., Eberhardt, S., Fischer, M., Kis, K., and Richter, G. (2000). Biosynthesis of vitamin B2 (riboflavin). Annu. Rev. Nutr.20, 153–167.10.1146/annurev.nutr.20.1.153Search in Google Scholar

Bacher, A., Eberhardt, S., Eisenreich, W., Fischer, M., Herz, S., Illarionov, B., Kis, K., and Richter, G. (2001). Biosynthesis of riboflavin. Vitam. Horm.61, 1–49.10.1016/S0083-6729(01)61001-XSearch in Google Scholar

Bullock, W.O., Fernandez, J.M., and Short, J.M. (1987). XL-blue: a high efficiency plasmid transforming recA Escherichia coli strain with β-galactosidase selection. Biotechniques5, 376–379.Search in Google Scholar

Burrows, R.B. and Brown, G.M. (1978). Presence of Escherichia coli of a deaminase and a reductase involved in biosynthesis of riboflavin. J. Bacteriol.136, 657–667.10.1128/jb.136.2.657-667.1978Search in Google Scholar PubMed PubMed Central

Christie, J.M., Salomon, M., Nozue, K., Wada, M., and Briggs, W.R. (1999). LOV (light, oxygen, or voltage) domains of the blue-light photoreceptor phototropin (nph1): binding sites for the chromophore flavin mononucleotide. Proc. Natl. Acad. Sci. USA96, 8779–8783.10.1073/pnas.96.15.8779Search in Google Scholar PubMed PubMed Central

Dayhoff, M.O. (1979). Atlas of Protein Sequence and Structure, Vol. 5 (Suppl. 3). (Washington, DC, USA: National Biomedical Research Foundation).Search in Google Scholar

Eberhardt, S., Zingler, N., Kemter, K., Richter, G., Cushman, M., and Bacher, A. (2001). Domain structure of riboflavin synthase. Eur. J. Biochem.268, 4315–4323.10.1046/j.1432-1327.2001.02351.xSearch in Google Scholar PubMed

Edman, P. and Henschen, A. (1975). Sequence determination. In: Protein Sequence Determination (Heidelberg, Germany: Springer Verlag).Search in Google Scholar

Felsenstein, J. (1985). Confidence limits on phylogenies: an approach using the bootstrap. Evolution39, 783–791.10.1111/j.1558-5646.1985.tb00420.xSearch in Google Scholar PubMed

Felsenstein, J. (1995). PHYLIP (Phylogeny Interference Package), Version 3.57c. (Distributed by the author). Department of Genetics, University of Washington, Seattle, WA, USA.Search in Google Scholar

Fischer, M., Haase, I., Feicht, R., Richter, G., Gerhardt, S., Changeux, J.P., Huber, R., and Bacher, A. (2002). Biosynthesis of riboflavin: 6,7-dimethyl-8-ribityllumazine synthase of Schizosaccharomyces pombe. Eur. J. Biochem.269, 519–526.10.1046/j.0014-2956.2001.02674.xSearch in Google Scholar PubMed

Fischer, M., Römisch, W., Saller, S., Illarionov, B., Richter, G., Rohdich, F., Eisenreich, W., and Bacher, A. (2004a). Evolution of vitamin B2 biosynthesis: structural and functional similarity between pyrimidine deaminases of eubacterial and plant origin. J. Biol. Chem.279, 36299–36308.10.1074/jbc.M404406200Search in Google Scholar

Fischer, M., Schott, A.K., Römisch, W., Ramsperger, A., Augustin, M., Fidler, A., Bacher, A., Richter, G., Huber, R., and Eisenreich, W. (2004b). Evolution of vitamin B2 biosynthesis. A novel class of riboflavin synthase in Archaea. J. Mol. Biol.343, 267–278.10.1016/j.jmb.2004.08.016Search in Google Scholar

Galtier, N., Gouy, M., and Gautier, C. (1996). SEAVIEW and PHYLO_WIN: Two graphic tools for sequence alignment and molecular phylogeny. Comput. Appl. Biosci.12, 543–548.10.1093/bioinformatics/12.6.543Search in Google Scholar

Gerhardt, S., Schott, A.K., Kairies, N., Cushman, M., Illarionov, B., Eisenreich, W., Bacher, A., Huber, R., Steinbacher, S., and Fischer, M. (2002). Studies on the reaction mechanism of riboflavin synthase: X-ray crystal structure of a complex with 6-carboxyethyl-7-oxo-8-ribityllumazine. Structure10, 1371–1381.10.1016/S0969-2126(02)00864-XSearch in Google Scholar

Graham, D.E., Xu, H., and White, R.H. (2002). A member of a new class of GTP cyclohydrolases produces formylaminopyrimidine nucleotide monophosphates. Biochemistry41, 15074–15084.10.1021/bi0268798Search in Google Scholar

Harvey, R.A. and Plaut, G.W. (1966). Riboflavin synthetase from yeast. Properties of complexes of the enzyme with lumazine derivatives and riboflavin. J. Biol. Chem.241, 2120–2136.10.1016/S0021-9258(18)96675-5Search in Google Scholar

Herz, S., Eberhardt, S., and Bacher, A. (2000). Biosynthesis of riboflavin in plants. The ribA gene of Arabidopsis thaliana specifies a bifunctional GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase. Phytochemistry53, 723–731.Search in Google Scholar

Hollander, I. and Brown, G.M. (1979). Biosynthesis of riboflavin: reductase and deaminase of Ashbya gossypii. Biochem. Biophys. Res. Commun.89, 759–763.10.1016/0006-291X(79)90694-6Search in Google Scholar

Huala, E., Oeller, P.W., Liscum, E., Han, I.S., Larsen, E., and Briggs, W.R. (1997). Arabidopsis NPH1: a protein kinase with a putative redox-sensing domain. Science278, 2120–2123.10.1126/science.278.5346.2120Search in Google Scholar PubMed

Illarionov, B., Eisenreich, W., and Bacher, A. (2001a). A pentacyclic reaction intermediate of riboflavin synthase. Proc. Natl. Acad. Sci. USA98, 7224–7229.10.1073/pnas.131610698Search in Google Scholar PubMed PubMed Central

Illarionov, B., Kemter, K., Eberhardt, S., Richter, G., Cushman, M., and Bacher, A. (2001b). Riboflavin synthase of Escherichia coli. Effect of single amino acid substitutions on reaction rate and ligand binding properties. J. Biol. Chem.276, 11524–11530.10.1074/jbc.M008931200Search in Google Scholar PubMed

Imada, Y., Iida, H., Ono, S., and Murahashi, S. (2003). Flavin catalyzed oxidations of sulfides and amines with molecular oxygen. J. Am. Chem. Soc.125, 2868–2869.10.1021/ja028276pSearch in Google Scholar

Jordan, D.B., Bacot, K.O., Carlson, T.J., Kessel, M., and Viitanen, P.V. (1999). Plant riboflavin biosynthesis. Cloning, chloroplast localization, expression, purification, and partial characterization of spinach lumazine synthase. J. Biol. Chem.274, 22114–22121.10.1074/jbc.274.31.22114Search in Google Scholar

Kane, J.F. (1995). Effects of rare codon clusters on high-level expression of heterologous proteins in Escherichia coli. Curr. Opin. Biotechnol.6, 494–500.10.1016/0958-1669(95)80082-4Search in Google Scholar

Kapatral, V., Anderson, I., Ivanova, N., Reznik, G., Los, T., Lykidis, A., Bhattacharyya, A., Bartman, A., Gardner, W., Grechkin, G., et al. (2002). Genome sequence and analysis of the oral bacterium Fusobacterium nucleatum strain ATCC 25586. J. Bacteriol.184, 2005–2018.10.1128/JB.184.7.2005-2018.2002Search in Google Scholar

Kis, K. and Bacher, A. (1995). Substrate channeling in the lumazine synthase/riboflavin synthase complex of Bacillus subtilis. J. Biol. Chem.270, 16788–16795.10.1074/jbc.270.28.16788Search in Google Scholar

Kurland, C. and Gallant, J. (1996). Errors of heterologous protein expression. Curr. Opin. Biotechnol.7, 489–493.10.1016/S0958-1669(96)80050-4Search in Google Scholar

Kuzmic, P. (1996). Program DYNAFIT for the analysis of enzyme kinetic data: application to HIV proteinase. Anal. Biochem.237, 260–273.10.1006/abio.1996.0238Search in Google Scholar

Ladenstein, R., Schneider, M., Huber, R., Bartunik, H.D., Wilson, K., Schott, K., and Bacher, A. (1988). Heavy riboflavin synthase from Bacillus subtilis. Crystal structure analysis of the icosahedral beta 60 capsid at 3.3 Å resolution. J. Mol. Biol.203, 1045–1070.10.1016/0022-2836(88)90128-3Search in Google Scholar

Laemmli, U.K. (1970). Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature227, 680–685.10.1038/227680a0Search in Google Scholar PubMed

Laue, T.M., Shah, B.D., Ridgeway, T.M., and Pelletier, S.L. (1992). Computer-aided interpretation of analytical sedimentation data for proteins. In: Analytical Ultracentrifugation in Biochemistry and Polymer Science, S.E. Harding, A.J. Rowe and J.C. Horton, eds. (Cambridge, UK: Royal Society of Chemistry), pp. 90–125.Search in Google Scholar

Li, Y.F. and Sancar, A. (1991). Cloning, sequencing, expression and characterization of DNA photolyase from Salmonella typhimurium. Nucleic Acids Res.19, 4885–4890.10.1093/nar/19.18.4885Search in Google Scholar PubMed PubMed Central

Liao, D.I., Wawrzak, Z., Calabrese, J.C., Viitanen, P.V., and Jordan, D.B. (2001). Crystal structure of riboflavin synthase. Structure9, 399–408.10.1016/S0969-2126(01)00600-1Search in Google Scholar

Lin, C., Robertson, D.E., Ahmad, M., Raibekas, A.A., Jorns, M.S., Dutton, P.L., and Cashmore, A.R. (1995). Association of flavin adenine dinucleotide with the Arabidopsis blue light receptor CRY1. Science269, 968–970.10.1126/science.7638620Search in Google Scholar

Maley, G.F. and Plaut, G.W. (1959). The isolation, synthesis, and metabolic properties of 6,7-dimethyl-8-ribityllumazine. J. Biol. Chem.243, 641–647.10.1016/S0021-9258(18)70261-5Search in Google Scholar

Mann, M. and Wilm, M. (1995). Electrospray mass spectrometry for protein characterization. Trends Biochem. Sci.20, 219–224.10.1016/S0968-0004(00)89019-2Search in Google Scholar

Meining, W., Tibbelin, G., Ladenstein, R., Eberhardt, S., Fischer, M., and Bacher, A. (1998). Evidence for local 32 symmetry in homotrimeric riboflavin synthase of Escherichia coli. J. Struct. Biol.121, 53–60.10.1006/jsbi.1997.3935Search in Google Scholar

Meining, W., Eberhardt, S., Bacher, A., and Ladenstein, R. (2003). The structure of the N-terminal domain of riboflavin synthase in complex with riboflavin at 2.6 Å resolution. J. Mol. Biol.331, 1053–1063.10.1016/S0022-2836(03)00844-1Search in Google Scholar

Mitsuda, H., Kawai, F., Suzuki, Y., and Yoshimoto, S. (1970). Biogenesis of riboflavin in green leaves. VII. Isolation and characterization of spinach riboflavin synthetase. J. Vitaminol. (Kyoto)16, 285–292.10.5925/jnsv1954.16.285Search in Google Scholar

Nakamura, Y., Gojobori, T., and Ikemura, T. (2000). Codon usage tabulated from international DNA sequence databases: status for the year 2000. Nucleic Acids Res.28, 292.10.1093/nar/28.1.292Search in Google Scholar

Nelson, K.E., Clayton, R.A., Gill, S.R., Gwinn, M.L., Dodson, R.J., Haft, D.H., Hickey, E.K., Peterson, J.D., Nelson, W.C., Ketchum, K.A., et al. (1999). Evidence for lateral gene transfer between Archaea and bacteria from genome sequence of Thermotoga maritima. Nature399, 323–329.10.1038/20601Search in Google Scholar

Neuberger, G. and Bacher, A. (1986). Biosynthesis of riboflavin. Enzymatic formation of 6,7-dimethyl-8-ribityllumazine by heavy riboflavin synthase from Bacillus subtilis. Biochem. Biophys. Res. Commun.139, 1111–1116.Search in Google Scholar

Nielsen, P. and Bacher, A. (1981). Biosynthesis of riboflavin. Characterization of the product of the deaminase. Biochim. Biophys. Acta662, 312–317.10.1016/0005-2744(81)90044-9Search in Google Scholar

Otto, M.K. and Bacher, A. (1981). Ligand-binding studies on light riboflavin synthase from Bacillus subtilis. Eur. J. Biochem.115, 511–517.10.1111/j.1432-1033.1981.tb06232.xSearch in Google Scholar

Persson, K., Schneider, G., Douglas, B.J., Viitanen, P.V., and Sandalova, T. (1999). Crystal structure analysis of a pentameric fungal and icosahedral plant lumazine synthase reveals the structural basis of differences in assembly. Protein Sci.8, 2355–2365.Search in Google Scholar

Plaut, G.W. (1963). Studies on the nature of the enzymic conversion of 6,7-dimethyl-8-ribityllumazine to riboflavin. J. Biol. Chem.238, 2225–2243.10.1016/S0021-9258(18)67964-5Search in Google Scholar

Plaut, G.W.E. and Harvey, R.A. (1971). The enzymatic synthesis of riboflavin. In: Methods in Enzymology, Volume 18, D.B. McCormick and L.D. Wright, eds. (New York, USA: Academic Press), pp. 515–538.10.1016/S0076-6879(71)18114-1Search in Google Scholar

Plaut, G.W., Beach, R.L., and Aogaichi, T. (1970). Studies on the mechanism of elimination of protons from the methyl groups of 6,7-dimethyl-8-ribityllumazine by riboflavin synthetase. Biochemistry9, 771–785.10.1021/bi00806a010Search in Google Scholar

Read, S.M. and Northcote, D.H. (1981). Minimization of variation in the response to different proteins of the Coomassie blue G dye-biding assay for protein. Anal. Biochem.116, 53–64.10.1016/0003-2697(81)90321-3Search in Google Scholar

Richter, G., Fischer, M., Krieger, C., Eberhardt, S., Lüttgen, H., Gerstenschläger, I., and Bacher, A. (1997). Biosynthesis of riboflavin: characterization of the bifunctional deaminase-reductase of Escherichia coli and Bacillus subtilis. J. Bacteriol.179, 2022–2028.10.1128/jb.179.6.2022-2028.1997Search in Google Scholar PubMed PubMed Central

Salomon, M., Eisenreich, W., Durr, H., Schleicher, E., Knieb, E., Massey, V., Rüdiger, W., Müller, F., Bacher, A., and Richter, G. (2001). An optomechanical transducer in the blue light receptor phototropin from Avena sativa. Proc. Natl. Acad. Sci. USA98, 12357–12361.10.1073/pnas.221455298Search in Google Scholar PubMed PubMed Central

Sanger, F., Niklen, S., and Coulson, A.R. (1977). DNA sequencing with chain-terminating inhibitors. Proc. Natl. Acad. Sci. USA74, 5463–5467.10.1073/pnas.74.12.5463Search in Google Scholar PubMed PubMed Central

Santos, M.A., Garcia-Ramirez, J.J., and Revuelta, J.L. (1995). Riboflavin biosynthesis in Saccharomyces cerevisiae. Cloning, characterization, and expression of the RIB5 gene encoding riboflavin synthase. J. Biol. Chem.270, 437–444.10.1074/jbc.270.1.437Search in Google Scholar PubMed

Schmidt, W. and Galland, P. (1999). Light-induced absorbance changes in Phycomyces: evidence for cryptochrome-associated flavosemiquinones. Planta208, 274–282.10.1007/s004250050559Search in Google Scholar PubMed

Schott, K., Kellermann, J., Lottspeich, F., and Bacher, A. (1990). Riboflavin synthases of Bacillus subtilis. Purification and amino acid sequence of the α subunit. J. Biol. Chem.265, 4204–4209.Search in Google Scholar

Stueber, D., Matile, H., and Garotta, G. (1990). System for high level production in E. coli and rapid purification of recombinant proteins: application to epitope mapping, preparation of antibodies and structure function analysis. In: Immunological Methods IV, I. Lefkovits and P. Pernis, eds. (New York, USA: Academic Press), pp. 121–125.Search in Google Scholar

Volk, R. and Bacher, A. (1988). Biosynthesis of riboflavin. The structure of the four-carbon precursor. J. Am. Chem. Soc.110, 3651–3653.Search in Google Scholar

Volk, R. and Bacher, A. (1990). Studies on the 4-carbon precursor in the biosynthesis of riboflavin. Purification and properties of L-3,4-dihydroxy-2-butanone-4-phosphate synthase. J. Biol. Chem.265, 19479–19485.Search in Google Scholar

Wacker, H., Harvey, R.A., Winestock, C.H., and Plaut, G.W. (1964). 4-(1′-D-Ribitylamino)-5-amino-2,6-dihydroxypyrimidine, the second product of the riboflavin synthetase reaction. J. Biol. Chem.239, 3493–3497.10.1016/S0021-9258(18)97749-5Search in Google Scholar

Young, D.W. (1986). The biosynthesis of the vitamins thiamin, riboflavin, and folic acid. Nat. Prod. Rep.3, 395–419.10.1039/np9860300395Search in Google Scholar PubMed

Zamenhof, P. and Villarejo, M. (1972). Construction and properties of Escherichia coli strains exhibiting α-complementation of β-galactosidase fragments in vivo. J. Bacteriol.110, 171–178.10.1128/jb.110.1.171-178.1972Search in Google Scholar PubMed PubMed Central

Zhou, Z., Schnake, P., Xiao, L., and Lal, A.A. (2004). Enhanced expression of a recombinant malaria candidate vaccine in Escherichia coli by codon optimization. Protein Expr. Purif.34, 87–94.10.1016/j.pep.2003.11.006Search in Google Scholar PubMed

Published Online: 2005-07-05
Published in Print: 2005-05-01

© Walter de Gruyter Berlin New York

Articles in the same Issue

  1. Saccharomyces cerevisiae translational activator Cbs1p is associated with translationally active mitochondrial ribosomes
  2. Evolution of vitamin B2 biosynthesis: riboflavin synthase of Arabidopsis thaliana and its inhibition by riboflavin
  3. Molecular basis of the complex formation between the two calcium-binding proteins S100A8 (MRP8) and S100A9 (MRP14)
  4. An extracellular carboxylesterase from the basidiomycete Pleurotus sapidus hydrolyses xanthophyll esters
  5. The composition, structural properties and binding of very-low-density and low-density lipoproteins to the LDL receptor in normo- and hypertriglyceridemia: relation to the apolipoprotein E phenotype
  6. Adrenodoxin (Adx) and CYP11A1 (P450scc) induce apoptosis by the generation of reactive oxygen species in mitochondria
  7. Ultraspiracle promotes the nuclear localization of ecdysteroid receptor in mammalian cells
  8. Polyadenylate polymerase modulations in human epithelioid cervix and breast cancer cell lines, treated with etoposide or cordycepin, follow cell cycle rather than apoptosis induction
  9. The anti-inflammatory compound curcumin inhibits Neisseria gonorrhoeae-induced NF-κB signaling, release of pro-inflammatory cytokines/chemokines and attenuates adhesion in late infection
  10. Susceptibility of the interchain peptide of a bromelain inhibitor precursor to the target proteases bromelain, chymotrypsin, and trypsin
  11. Blocking effect of a biotinylated protease inhibitor on the egress of Plasmodium falciparum merozoites from infected red blood cells
https://doi.org/10.1515/BC.2005.050
Keywords for this article
analytical ultracentrifugation; circular dichroism spectroscopy; kinetic analysis; phylogenetic analysis; plant; synthetic gene

Articles in the same Issue

  1. Saccharomyces cerevisiae translational activator Cbs1p is associated with translationally active mitochondrial ribosomes
  2. Evolution of vitamin B2 biosynthesis: riboflavin synthase of Arabidopsis thaliana and its inhibition by riboflavin
  3. Molecular basis of the complex formation between the two calcium-binding proteins S100A8 (MRP8) and S100A9 (MRP14)
  4. An extracellular carboxylesterase from the basidiomycete Pleurotus sapidus hydrolyses xanthophyll esters
  5. The composition, structural properties and binding of very-low-density and low-density lipoproteins to the LDL receptor in normo- and hypertriglyceridemia: relation to the apolipoprotein E phenotype
  6. Adrenodoxin (Adx) and CYP11A1 (P450scc) induce apoptosis by the generation of reactive oxygen species in mitochondria
  7. Ultraspiracle promotes the nuclear localization of ecdysteroid receptor in mammalian cells
  8. Polyadenylate polymerase modulations in human epithelioid cervix and breast cancer cell lines, treated with etoposide or cordycepin, follow cell cycle rather than apoptosis induction
  9. The anti-inflammatory compound curcumin inhibits Neisseria gonorrhoeae-induced NF-κB signaling, release of pro-inflammatory cytokines/chemokines and attenuates adhesion in late infection
  10. Susceptibility of the interchain peptide of a bromelain inhibitor precursor to the target proteases bromelain, chymotrypsin, and trypsin
  11. Blocking effect of a biotinylated protease inhibitor on the egress of Plasmodium falciparum merozoites from infected red blood cells
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