Genomes and Genes
Gene Symbol: lef
Description: lethal factor
Species: Bacillus anthracis str. 'Ames Ancestor'
- Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factorN S Duesbery
Advanced BioScience Laboratories Basic Research Program, National Cancer Institute Frederick Cancer Research and Development Center, Post Office Box B, Frederick, MD 21702
Science 280:734-7. 1998..The identification of a cleavage site for LF may facilitate the development of LF inhibitors...
- Anthrax lethal factor cleaves the N-terminus of MAPKKs and induces tyrosine/threonine phosphorylation of MAPKs in cultured macrophagesG Vitale
Dipartimento di Scienze Biomediche, Universita di Padova, Italy
Biochem Biophys Res Commun 248:706-11. 1998..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...
- Anthrax lethal toxin enhances TNF-induced endothelial VCAM-1 expression via an IFN regulatory factor-1-dependent mechanismJason M Warfel
Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20892
J Immunol 180:7516-24. 2008..Altering the activity of key transcription factors involved in host response to infection may be a critical mechanism by which LT contributes to anthrax pathogenesis...
- Vector-mediated selective expression of lethal factor, a toxic element of Bacillus anthracis, damages A549 cells via inhibition of MAPK and AKT pathwaysWenlei Zhuo
Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
Int J Med Sci 10:292-8. 2013..The results also revealed that the inhibition of mitogen-activated protein kinase and AKT pathways was partially involved in the process. Thus, hTERTp-regulated LF increase could be a promising approach in lung cancer-targeted therapy...
- Expression of either lethal toxin or edema toxin by Bacillus anthracis is sufficient for virulence in a rabbit model of inhalational anthraxJulie A Lovchik
Center for Infectious Disease and Immunity, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA
Infect Immun 80:2414-25. 2012..Ames strain versus isogenic mutants with deletions of the genes for the capsule operon (capBCADE), lethal factor (lef), edema factor (cya), or protective antigen (pagA)...
- Effect of pH on the catalytic function and zinc content of native and immobilized anthrax lethal factorLise H Montpellier
Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ontario, Canada
FEBS Lett 587:317-21. 2013....
- Anthrax toxin-induced shock in rats is associated with pulmonary edema and hemorrhageShu Ru Kuo
Cancer Research Institute, Scott and White Memorial Hospital, Temple, TX 76502, USA
Microb Pathog 44:467-72. 2008..These observations provide a rational basis for drug interventions to reduce the effect of these toxins on the heart and blood vessels...
- Efficient production and characterization of Bacillus anthracis lethal factor and a novel inactive mutant rLFm-Y236FSha Cao
National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China
Protein Expr Purif 59:25-30. 2008..This mutant might be of significance in the study of anthrax pathogenesis and treatment...
- COPI coatomer complex proteins facilitate the translocation of anthrax lethal factor across vesicular membranes in vitroAlfred G Tamayo
Section of Molecular Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
Proc Natl Acad Sci U S A 105:5254-9. 2008..This facilitated delivery appears to use a mechanism that is analogous to that of DT entry...
- Intrinsic curvature associated with the coordinately regulated anthrax toxin gene promotersMaria Hadjifrangiskou
Department of Microbiology and Molecular Genetics, University of Texas Houston Health Science Center, 6431 Fannin Street, Houston, TX 77030, USA
Microbiology 154:2501-12. 2008..AtxA is a positive regulator of the toxin genes pagA, cya and lef, and of a number of other plasmid- and chromosome-encoded genes...
- Computational insights into the interaction of the anthrax lethal factor with the N-terminal region of its substratesManali Joshi
Department of Biology and Biochemistry, University of Houston, Houston, Texas 77204 5001, USA
Proteins 75:323-35. 2009..On the basis of the results, we conclude that the LF does not equally accommodate the MEK substrates and further predict that there will be differences between rates of cleavage among the nine residue MEK N-termini...
- Induction of autophagy by anthrax lethal toxinYian Kim Tan
Molecular and Microbiology Department, College of Sciences, George Mason University, Manassas, VA 22010, USA
Biochem Biophys Res Commun 379:293-7. 2009..This study presents a hitherto undescribed effect of LT-induced autophagy on cells and provides the groundwork for future studies on the implication of autophagy in anthrax pathogenesis...
- Bacillus anthracis edema toxin suppresses human macrophage phagocytosis and cytoskeletal remodeling via the protein kinase A and exchange protein activated by cyclic AMP pathwaysLinsey A Yeager
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555 0610, USA
Infect Immun 77:2530-43. 2009..These results suggested that EdTx weakened the host immune response by increasing cAMP levels, which then signaled via PKA and Epac to cripple MPhi phagocytosis and interfered with cytoskeletal remodeling...
- Anthrax lethal toxin impairs IL-8 expression in epithelial cells through inhibition of histone H3 modificationBenoit Raymond
Institut Pasteur, Unité de Défense Innée et Inflammation, Paris, France
PLoS Pathog 5:e1000359. 2009..This epigenetic reprogramming, in addition to previously reported effects of LT, may represent an efficient strategy used by B. anthracis for invading the host...
- Bacillus anthracis edema toxin impairs neutrophil actin-based motilitySarah E Szarowicz
Division of Infectious Diseases, University of Florida College of Medicine, Gainesville, FL 32610, USA
Infect Immun 77:2455-64. 2009..We conclude that ET alone or combined with LT impairs PMN actin assembly, resulting in paralysis of PMN chemotaxis...
- Substrate recognition of anthrax lethal factor examined by combinatorial and pre-steady-state kinetic approachesMaria Yu Zakharova
M M Shemyakin and Yu A Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997
J Biol Chem 284:17902-13. 2009..Based on the available structural and kinetic data, we propose a model for LF-substrate interaction. Resolution of the kinetic and structural parameters governing LF activity may be exploited to design new LF inhibitors...
- The major neutralizing antibody responses to recombinant anthrax lethal and edema factors are directed to non-cross-reactive epitopesMelissa L Nguyen
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA
Infect Immun 77:4714-23. 2009..This work increases understanding of the immunogenicity of EF and LF and offers perspective for the development of new strategies for vaccination against anthrax...
- Use of allostery to identify inhibitors of calmodulin-induced activation of Bacillus anthracis edema factorElodie Laine
Institut Pasteur, Unité de Bioinformatique Structurale and Centre National de la Recherche Scientifique, Unité de Recherche Associée 2185, 25 28, rue du Dr Roux, 75 724 Paris, France
Proc Natl Acad Sci U S A 107:11277-82. 2010..The specific homology between the putative allosteric sites in both toxins supports that these pockets are the actual binding sites of the selected inhibitors...
- Contribution of lethal toxin and edema toxin to the pathogenesis of anthrax meningitisCelia M Ebrahimi
Department of Biology and Center for Microbial Sciences, San Diego State University, 5500 Campanile Dr, San Diego, California 92182 4614, USA
Infect Immun 79:2510-8. 2011..Finally, in a murine model of anthrax meningitis, mice infected with the ΔLF mutant exhibited no mortality, brain bacterial load, or evidence of meningitis compared to mice infected with the parental or ΔEF strains...
- Lethal factor is not required for Bacillus anthracis virulence in guinea pigs and rabbitsHaim Levy
Department of Infectious Diseases, Israel Institute for Biological Research, 74100 Ness Ziona, Israel
Microb Pathog 51:345-51. 2011..Deletion of this gene (lef) in the Sterne strain was reported to dramatically reduce the pathogenicity of this strain in mice, and was ..
- Anthrax edema toxin sensitizes DBA/2J mice to lethal toxinAaron M Firoved
National Institute of Allergy and Infectious Diseases, National Institutes of Health, 30 Convent Dr, Building 30, Room 303, Bethesda, MD 20892 4349, USA
Infect Immun 75:2120-5. 2007..g., 15 microg) given to male and female DBA/2J mice 18 h prior to LT challenge also sensitize them to LT. This study using highly purified ET and LT demonstrates how the components of anthrax toxin can work together to increase lethality...
- Efficient synthetic inhibitors of anthrax lethal factorMartino Forino
Burnham Institute, Cancer Research Center and Infectious and Inflammatory Disease Center, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 102:9499-504. 2005..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...
- Zinc content of the Bacillus anthracis lethal factorS K Kochi
Laboratoire de Génétique Moléculaire des Toxines URA 557, CNRS, Institut Pasteur, Paris, France
FEMS Microbiol Lett 124:343-8. 1994..Using a large array of protease model substrates, however, we were unable to detect an endogenous protease activity for lethal factor...
- The three Bacillus anthracis toxin genes are coordinately regulated by bicarbonate and temperatureJ C Sirard
Laboratoire de Génétique Moléculaire des Toxines URA 1858, Centre National de la Recherche Scientifique, Institut Pasteur, Paris, France
J Bacteriol 176:5188-92. 1994..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...
- Secondary structure of anthrax lethal toxin proteins and their interaction with large unilamellar vesicles: a fourier-transform infrared spectroscopy approachX M Wang
Laboratoire de Chimie Physique des Macromolecules aux Interfaces, Universite Libre de Bruxelles, Belgium
Biochemistry 35:14939-46. 1996....
- Lethal factor active-site mutations affect catalytic activity in vitroS E Hammond
Department of Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA
Infect Immun 66:2374-8. 1998..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...
- Proteasome activity is required for anthrax lethal toxin to kill macrophagesG Tang
Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA
Infect Immun 67:3055-60. 1999..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...
- Anthrax lethal factor causes proteolytic inactivation of mitogen-activated protein kinase kinaseN S Duesbery
ABL Basic Research Program, NCI FCRDC, Frederick, MD 21702, USA
J Appl Microbiol 87:289-93. 1999..The consequences of this inactivation upon meiosis and transformed cells are also discussed...
- Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factorG Vitale
Centro CNR Biomembrane and Dipartimento di Scienze Biomediche, Universita di Padova, Via Trieste 75, 35121 Padova, Italy
Biochem J 352:739-45. 2000..The implications of these findings for the biochemical activity and functional specificity of LF are discussed...
- Involvement of residues 147VYYEIGK153 in binding of lethal factor to protective antigen of Bacillus anthracisP Gupta
Centre for Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India
Biochem Biophys Res Commun 280:158-63. 2001..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...
- Toxins of Bacillus anthracisF Brossier
Unité des Toxines et Pathogénie Bactériennes URA CNRS 2172, Institut Pasteur, 28 rue du Docteur Roux, 75725 15, Paris Cedex, France
Toxicon 39:1747-55. 2001..Progress in the structure-function relationship of these three proteins, their regulation mechanisms and their roles in pathogenesis and immunoprotection will be exposed...
- Crystal structure of the anthrax lethal factorA D Pannifer
Biochemistry Department, University of Leicester, Leicester LE1 7RH, UK
Nature 414:229-33. 2001..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...
- Sequence analysis of the genes encoding for the major virulence factors of Bacillus anthracis vaccine strain 'Carbosap'R Adone
Laboratorio di Medicina Veterinaria, Istituto Superiore di Sanita, Rome, Italy
J Appl Microbiol 93:117-21. 2002..anthracis strain, to evaluate the basis of attenuation...
- Asp 187 and Phe 190 residues in lethal factor are required for the expression of anthrax lethal toxin activityAparna Singh
Centre for Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India
FEMS Microbiol Lett 212:183-6. 2002..Their protective antigen-binding ability was drastically reduced. We propose that Asp187 and Phe190 are crucial for the expression of anthrax lethal toxin activity...
- The structural basis for substrate and inhibitor selectivity of the anthrax lethal factorBenjamin E Turk
Division of Signal Transduction, Department of Medicine, Beth Israel Deaconess Medical Center, and Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA
Nat Struct Mol Biol 11:60-6. 2004..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...
- Identification of small molecule inhibitors of anthrax lethal factorRekha G Panchal
Developmental Therapeutics Program, NCI Frederick, Frederick, Maryland 21702 1201, USA
Nat Struct Mol Biol 11:67-72. 2004..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...
- Large-scale structural changes accompany binding of lethal factor to anthrax protective antigen: a cryo-electron microscopic studyGang Ren
Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Structure 12:2059-66. 2004..The observed structural reorganization in PA63h likely facilitates the passage of the large 90 kDa LF molecule through the lumen en route to its eventual delivery across the membrane bilayer...
- Inhibition of Bacillus anthracis growth and virulence-gene expression by inhibitors of quorum-sensingMarcus B Jones
Department of Microbiology, Sackler Institute, and Department of Medicine, New York University School of Medicine, New York, New York 10016, USA
J Infect Dis 191:1881-8. 2005..We studied the effects on Bacillus anthracis growth and the virulence gene (pagA, lef, and cya) expression of the QS inhibitor (5Z)-4-bromo-5-(bromomethylene)-3-butyl-2(5H)-furanone, which is naturally ..
- Anthrax lethal factor inhibitionW L Shoop
Merck Research Laboratories, Rahway, NJ 07065, USA
Proc Natl Acad Sci U S A 102:7958-63. 2005..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...
- Nucleotide sequence and analysis of the lethal factor gene (lef) from Bacillus anthracisT S Bragg
Department of Chemistry, Brigham Young University, Provo, UT 84602
Gene 81:45-54. 1989The nucleotide sequence of the Bacillus anthracis lethal factor (LF) gene (lef) has been determined. LF is part of the tripartite protein exotoxin of B. anthracis along with protective antigen (PA) and edema factor (EF)...