pxo1_107

Summary

Gene Symbol: pxo1_107
Description: pXO1-107
Species: anthrax
Products:     pxo1_107

Top Publications

  1. Panchal R, Hermone A, Nguyen T, Wong T, Schwarzenbacher R, Schmidt J, et al. Identification of small molecule inhibitors of anthrax lethal factor. Nat Struct Mol Biol. 2004;11:67-72 pubmed publisher
    ..Three of these compounds have K(i) values in the 0.5-5 microM range and show competitive inhibition. These molecular scaffolds may be used to develop therapeutically viable inhibitors of LF...
  2. Singh A, Chauhan V, Sodhi A, Bhatnagar R. Asp 187 and Phe 190 residues in lethal factor are required for the expression of anthrax lethal toxin activity. FEMS Microbiol Lett. 2002;212:183-6 pubmed
    ..Their protective antigen-binding ability was drastically reduced. We propose that Asp187 and Phe190 are crucial for the expression of anthrax lethal toxin activity. ..
  3. Duesbery N, Webb C, Leppla S, Gordon V, Klimpel K, Copeland T, et al. Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science. 1998;280:734-7 pubmed
    ..The identification of a cleavage site for LF may facilitate the development of LF inhibitors...
  4. Adone R, Pasquali P, La Rosa G, Marianelli C, Muscillo M, Fasanella A, et al. Sequence analysis of the genes encoding for the major virulence factors of Bacillus anthracis vaccine strain 'Carbosap'. J Appl Microbiol. 2002;93:117-21 pubmed
    ..This paper adds new information regarding the molecular characteristics of the vaccine strain 'Carbosap' and highlights the need to better understand the virulence factors involved in the pathogenicity of B. anthracis strains...
  5. Tang G, Leppla S. Proteasome activity is required for anthrax lethal toxin to kill macrophages. Infect Immun. 1999;67:3055-60 pubmed
    ..Moreover, this proteasome-dependent process is an early step in LeTx intoxication, but it is downstream of the cleavage by LF of MEK1 or other putative substrates...
  6. Duesbery N, Vande Woude G. Anthrax lethal factor causes proteolytic inactivation of mitogen-activated protein kinase kinase. J Appl Microbiol. 1999;87:289-93 pubmed
    ..The consequences of this inactivation upon meiosis and transformed cells are also discussed...
  7. Bragg T, Robertson D. Nucleotide sequence and analysis of the lethal factor gene (lef) from Bacillus anthracis. Gene. 1989;81:45-54 pubmed
    ..The N-terminus of LF (first 300 aa) shared extensive homology with the N-terminus of the anthrax EF protein. Since LF and EF each bind PA at the same site, these homologous regions probably represent their common PA-binding domains...
  8. Vitale G, Bernardi L, Napolitani G, Mock M, Montecucco C. Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor. Biochem J. 2000;352 Pt 3:739-45 pubmed
    ..The implications of these findings for the biochemical activity and functional specificity of LF are discussed...
  9. Forino M, Johnson S, Wong T, Rozanov D, Savinov A, Li W, et al. Efficient synthetic inhibitors of anthrax lethal factor. Proc Natl Acad Sci U S A. 2005;102:9499-504 pubmed publisher
    ..Our data strongly indicate that the scaffold of inhibitors we have identified is the foundation for the development of novel, safe, and effective emergency therapy of postexposure inhalation anthrax...
  10. Brossier F, Mock M. Toxins of Bacillus anthracis. Toxicon. 2001;39:1747-55 pubmed
    ..Progress in the structure-function relationship of these three proteins, their regulation mechanisms and their roles in pathogenesis and immunoprotection will be exposed...

Detail Information

Publications19

  1. Panchal R, Hermone A, Nguyen T, Wong T, Schwarzenbacher R, Schmidt J, et al. Identification of small molecule inhibitors of anthrax lethal factor. Nat Struct Mol Biol. 2004;11:67-72 pubmed publisher
    ..Three of these compounds have K(i) values in the 0.5-5 microM range and show competitive inhibition. These molecular scaffolds may be used to develop therapeutically viable inhibitors of LF...
  2. Singh A, Chauhan V, Sodhi A, Bhatnagar R. Asp 187 and Phe 190 residues in lethal factor are required for the expression of anthrax lethal toxin activity. FEMS Microbiol Lett. 2002;212:183-6 pubmed
    ..Their protective antigen-binding ability was drastically reduced. We propose that Asp187 and Phe190 are crucial for the expression of anthrax lethal toxin activity. ..
  3. Duesbery N, Webb C, Leppla S, Gordon V, Klimpel K, Copeland T, et al. Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science. 1998;280:734-7 pubmed
    ..The identification of a cleavage site for LF may facilitate the development of LF inhibitors...
  4. Adone R, Pasquali P, La Rosa G, Marianelli C, Muscillo M, Fasanella A, et al. Sequence analysis of the genes encoding for the major virulence factors of Bacillus anthracis vaccine strain 'Carbosap'. J Appl Microbiol. 2002;93:117-21 pubmed
    ..This paper adds new information regarding the molecular characteristics of the vaccine strain 'Carbosap' and highlights the need to better understand the virulence factors involved in the pathogenicity of B. anthracis strains...
  5. Tang G, Leppla S. Proteasome activity is required for anthrax lethal toxin to kill macrophages. Infect Immun. 1999;67:3055-60 pubmed
    ..Moreover, this proteasome-dependent process is an early step in LeTx intoxication, but it is downstream of the cleavage by LF of MEK1 or other putative substrates...
  6. Duesbery N, Vande Woude G. Anthrax lethal factor causes proteolytic inactivation of mitogen-activated protein kinase kinase. J Appl Microbiol. 1999;87:289-93 pubmed
    ..The consequences of this inactivation upon meiosis and transformed cells are also discussed...
  7. Bragg T, Robertson D. Nucleotide sequence and analysis of the lethal factor gene (lef) from Bacillus anthracis. Gene. 1989;81:45-54 pubmed
    ..The N-terminus of LF (first 300 aa) shared extensive homology with the N-terminus of the anthrax EF protein. Since LF and EF each bind PA at the same site, these homologous regions probably represent their common PA-binding domains...
  8. Vitale G, Bernardi L, Napolitani G, Mock M, Montecucco C. Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor. Biochem J. 2000;352 Pt 3:739-45 pubmed
    ..The implications of these findings for the biochemical activity and functional specificity of LF are discussed...
  9. Forino M, Johnson S, Wong T, Rozanov D, Savinov A, Li W, et al. Efficient synthetic inhibitors of anthrax lethal factor. Proc Natl Acad Sci U S A. 2005;102:9499-504 pubmed publisher
    ..Our data strongly indicate that the scaffold of inhibitors we have identified is the foundation for the development of novel, safe, and effective emergency therapy of postexposure inhalation anthrax...
  10. Brossier F, Mock M. Toxins of Bacillus anthracis. Toxicon. 2001;39:1747-55 pubmed
    ..Progress in the structure-function relationship of these three proteins, their regulation mechanisms and their roles in pathogenesis and immunoprotection will be exposed...
  11. Hammond S, Hanna P. Lethal factor active-site mutations affect catalytic activity in vitro. Infect Immun. 1998;66:2374-8 pubmed
    ..In contrast, the protease inhibitors bestatin and lysine CMK, previously shown to block LF activity on macrophages, did not block LF activity in vitro. These data provide the first direct evidence that LF may act as an endopeptidase...
  12. Wang X, Mock M, Ruysschaert J, Cabiaux V. Secondary structure of anthrax lethal toxin proteins and their interaction with large unilamellar vesicles: a fourier-transform infrared spectroscopy approach. Biochemistry. 1996;35:14939-46 pubmed
  13. Kochi S, Schiavo G, Mock M, Montecucco C. Zinc content of the Bacillus anthracis lethal factor. FEMS Microbiol Lett. 1994;124:343-8 pubmed
    ..Using a large array of protease model substrates, however, we were unable to detect an endogenous protease activity for lethal factor...
  14. Gupta P, Singh A, Chauhan V, Bhatnagar R. Involvement of residues 147VYYEIGK153 in binding of lethal factor to protective antigen of Bacillus anthracis. Biochem Biophys Res Commun. 2001;280:158-63 pubmed
    ..1 cells and their binding ability to PA63 was drastically reduced. We propose that these four amino acids play a crucial role in the process of binding of LF to PA63. ..
  15. Vitale G, Pellizzari R, Recchi C, Napolitani G, Mock M, Montecucco C. Anthrax lethal factor cleaves the N-terminus of MAPKKs and induces tyrosine/threonine phosphorylation of MAPKs in cultured macrophages. Biochem Biophys Res Commun. 1998;248:706-11 pubmed publisher
    ..The possible implications of these findings for the cytolysis of macrophage cells induced by LF are discussed. These results open the way to the design and screening of specific inhibitors of LF...
  16. Pannifer A, Wong T, Schwarzenbacher R, Renatus M, Petosa C, Bienkowska J, et al. Crystal structure of the anthrax lethal factor. Nature. 2001;414:229-33 pubmed publisher
    ..The structure thus reveals a protein that has evolved through a process of gene duplication, mutation and fusion, into an enzyme with high and unusual specificity...
  17. Turk B, Wong T, Schwarzenbacher R, Jarrell E, Leppla S, Collier R, et al. The structural basis for substrate and inhibitor selectivity of the anthrax lethal factor. Nat Struct Mol Biol. 2004;11:60-6 pubmed publisher
    ..The crystal structures of LF bound to an optimized peptide substrate and to peptide-based inhibitors provide a rationale for the observed selectivity and may be exploited in the design of future generations of LF inhibitors...
  18. Sirard J, Mock M, Fouet A. The three Bacillus anthracis toxin genes are coordinately regulated by bicarbonate and temperature. J Bacteriol. 1994;176:5188-92 pubmed
    ..Two environmental factors, bicarbonate and temperature, were found to induce beta-galactosidase synthesis in each recombinant strain. Furthermore, the transcription of the three toxin genes appears to be coordinately regulated...
  19. Shoop W, Xiong Y, Wiltsie J, Woods A, Guo J, Pivnichny J, et al. Anthrax lethal factor inhibition. Proc Natl Acad Sci U S A. 2005;102:7958-63 pubmed publisher
    ..These results indicate that a small molecule, hydroxamate LF inhibitor, as revealed herein, can ameliorate the toxemia characteristic of an active B. anthracis infection and could be a vital adjunct to our ability to combat anthrax...