The anthrax lethal factor and its MAPK kinase-specific metalloprotease activity

Molecular Aspects of Medicine

Volumn 30, Issue 6, 2009, Pages 431-438

  Tonello, Fiorella ^a   Montecucco, Cesare ^a  

^a UNIVERSITY OF PADOVA   (Italy)

Author keywords

Anthrax; Botulinum neurotoxins; Lethal factor; MAPK kinase; Metalloprotease

Indexed keywords

ANTHRAX TOXIN; CELL RECEPTOR; METALLOPROTEINASE; MITOGEN ACTIVATED PROTEIN KINASE; NEUROTOXIN;

AMINO TERMINAL SEQUENCE; ANTHRAX; BACILLUS ANTHRACIS; CELL PERMEABILIZATION; CLOSTRIDIUM; CRYSTALLOGRAPHY; CYTOSOL; ENZYME ACTIVITY; ENZYME SPECIFICITY; LETHAL GENE; NONHUMAN; PROTEIN CLEAVAGE; PROTEIN DEGRADATION; PROTEIN DOMAIN; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; ANTHRAX; ANTIGENS, BACTERIAL; BACILLUS ANTHRACIS; BACTERIAL TOXINS; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; METALLOPROTEASES; MITOGEN-ACTIVATED PROTEIN KINASE KINASES; MODELS, MOLECULAR; PROTEIN CONFORMATION;

BACILLUS ANTHRACIS;

EID: 70350733498     PISSN: 00982997     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.mam.2009.07.006     Document Type: Review

References (76)

1. Agrawal A., de Oliveira C.A., Cheng Y., Jacobsen J.A., McCammon J.A., and Cohen S.M. Thioamide hydroxypyrothiones supersede amide hydroxypyrothiones in potency against anthrax lethal factor. J. Med. Chem. 52 (2009) 1063-1074
2. Arora N., and Leppla S.H. Fusions of anthrax toxin lethal factor with shiga toxin and diphtheria toxin enzymatic domains are toxic to mammalian cells. Infect. Immun. 62 (1994) 4955-4961
3. Arora N., Williamson L.C., Leppla S.H., and Halpern J.L. Cytotoxic effects of a chimeric protein consisting of tetanus toxin light chain and anthrax toxin lethal factor in non-neuronal cells. J. Biol. Chem. 269 (1994) 26165-26171
4. Ascenzi P., Visca P., Ippolito G., Spallarossa A., Bolognesi M., and Montecucco C. Anthrax toxin: a tripartite lethal combination. FEBS Lett. 531 (2002) 384-388
5. Baldari C.T., Tonello F., Paccani S.R., and Montecucco C. Anthrax toxins: a paradigm of bacterial immune suppression. Trends Immunol. 27 (2006) 434-440
6. Ballard J., Collier R., and Starnbach M. Anthrax toxin-mediated delivery of a cytotoxic T-cell epitope in vivo. Proc. Natl. Acad. Sci. USA 93 (1996) 12531-12534
7. Bardwell L., and Thorner J. A conserved motif at the amino termini of MEKs might mediate high-affinity interaction with the cognate MAPKs. Trends Biochem. Sci. 21 (1996) 373-374
8. Bardwell A., Flatauer L.J., Matsukuma K., Thorner J., and Bardwell L. A conserved docking site in MEKs mediates high-affinity binding to MAP kinases and operates with a scaffold protein to enhance signal transmission. J. Biol. Chem. 276 (2001) 19374-19386
9. Bardwell A., Abdollahi M., and Bardwell L. Anthrax lethal factor-cleavage products of MAPK (mitogen-activated protein kinase) kinases exhibit reduced binding to their cognate MAPKs. Biochem. J. 378 (2004) 569-577
10. Beall F., Taylor M., and Thorne C. Rapid lethal effect in rats of a third component found upon fractionating the toxin of Bacillus anthracis. J. Bacteriol. 83 (1962) 1274-1280
11. Bromberg-White J.L., and Duesbery N.S. Biological and biochemical characterization of anthrax lethal factor, a proteolytic inhibitor of MEK signaling pathways. Methods Enzymol. 438 (2008) 355-365
12. Chauhan V., and Bhatnagar R. Identification of amino acid residues of anthrax protective antigen involved in binding with lethal factor. Infect. Immun. 70 (2002) 4477-4484
13. Chopra A., Boone S., Liang X., and Duesbery N. Anthrax lethal factor proteolysis and inactivation of MAPK kinase. J. Biol. Chem. 278 (2003) 9402-9406
14. Cummings R.T., Salowe S.P., Cunningham B.R., Wiltsie J., Park Y.W., Sonatore L.M., Wisniewski D., Douglas C.M., Hermes J.D., and Scolnick E.M. A peptide-based fluorescence resonance energy transfer assay for Bacillus anthracis lethal factor protease. Proc. Natl. Acad. Sci. USA 99 (2002) 6603-6606
15. Cunningham K., Lacy D., Mogridge J., and Collier R. Mapping the lethal factor and edema factor binding sites on oligomeric anthrax protective antigen. Proc. Natl. Acad. Sci. USA 99 (2002) 7049-7053
16. Dal Molin F., Tonello F., Ladant D., Zornetta I., Zamparo I., Di Benedetto G., Zaccolo M., and Montecucco C. Cell entry and cAMP imaging of anthrax edema toxin. EMBO J. 25 (2006) 5405-5413
17. Dalkas G., Papakyriakou A., Vlamis-Gardikas A., and Spyroulias G. Low molecular weight inhibitors of the protease anthrax lethal factor. Mini Rev. Med. Chem. 8 (2008) 290-306
18. Dalkas G., Papakyriakou A., Vlamis-Gardikas A., and Spyroulias G. Insights into the anthrax lethal factor-substrate interaction and selectivity using docking and molecular dynamics simulations. Protein Sci. 18 (2009) 1774-1785
19. Dell'Aica I., Donà M., Tonello F., Piris A., Mock M., Montecucco C., and Garbisa S. Potent inhibitors of anthrax lethal factor from green tea. EMBO Rep. 5 (2004) 418-422
20. Duesbery N.S., Webb C.P., Leppla S.H., Gordon V.M., Klimpel K.R., Copeland T.D., Ahn N.G., Oskarsson M.K., Fukasawa K., Paull K.D., and Vande Woude G.F. Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science 280 (1998) 734-737
21. Duesbury N.S., and Vande Woude G.F. Anthrax toxins. Cell. Mol. Life. Sci. 55 (1999) 1599-1609
22. Forino M., Johnson S., Wong T.Y., Rozanov D.V., Savinov A.Y., Li W., Fattorusso R., Becattini B., Orry A.J., Jung D., Abagyan R.A., Smith J.W., Alibek K., Liddington R.C., Strongin A.Y., and Pellecchia M. Efficient synthetic inhibitors of anthrax lethal factor. Proc. Natl. Acad. Sci. USA 102 (2005) 9499-9504
23. Fridman M., Belakhov V., Lee L., Liang F., Wong C., and Baasov T. Dual effect of synthetic aminoglycosides: antibacterial activity against Bacillus anthracis and inhibition of anthrax lethal factor. Angew. Chem. Int. Ed. Engl. 44 (2005) 447-452
24. Gaddis B.D., Rubert Pérez C.M., and Chmielewski J. Inhibitors of anthrax lethal factor based upon N-oleoyldopamine. Bioorg. Med. Chem. Lett. 18 (2008) 2467-2470
25. Gibrat J., Madej T., and Bryant S. Surprising similarities in structure comparison. Curr. Opin. Struct. Biol. 6 (1996) 377-385
26. Gill D., and Meren R. ADP-ribosylation of membrane proteins catalyzed by cholera toxin: basis of the activation of adenylate cyclase. Proc. Natl. Acad. Sci. USA 75 (1978) 3050-3054
27. Gupta P., Moayeri M., Crown D., Fattah R., and Leppla S. Role of N-terminal amino acids in the potency of anthrax lethal factor. PLoS One 3 (2008) e3130
28. Holmquist B., and Vallee B. Metal substitutions and inhibition of thermolysin: spectra of the cobalt enzyme. J. Biol. Chem. 249 (1974) 4601-4607
29. Hudson M., Beyer W., Böhm R., Fasanella A., Garofolo G., Golinski R., Goossens P., Hahn U., Hallis B., King A., Mock M., Montecucco C., Ozin A., Tonello F., and Kaufmann S. Bacillus anthracis: balancing innocent research with dual-use potential. Int. J. Med. Microbiol. 298 (2008) 345-364
30. Johnson S.L., Chen L.H., and Pellecchia M. A high-throughput screening approach to anthrax lethal factor inhibition. Bioorg. Chem. 35 (2007) 306-312
31. Johnson S.L., Chen L.H., Barile E., Emdadi A., Sabet M., Yuan H., Wei J., Guiney D., and Pellecchia M. Structure-activity relationship studies of a novel series of anthrax lethal factor inhibitors. Bioorg. Med. Chem. 17 (2009) 3352-3368
32. Katada T., and Ui M. Effect of in vivo pretreatment of rats with a new protein purified from Bordetella pertussis on in vitro secretion of insulin: role of calcium. Endocrinology 104 (1979) 1822-1827
33. Kim C., Gajendran N., Mittrucker H.W., Weiwad M., Song Y.H., Hurwitz R., Wilmanns M., Fischer G., and Kaufmann S.H. Human alpha-defensins neutralize anthrax lethal toxin and protect against its fatal consequences. Proc. Natl. Acad. Sci. USA 102 (2005) 4830-4835
34. Klimpel K.R., Arora N., and Leppla S.H. Anthrax toxin lethal factor contains a zinc metalloprotease consensus sequence which is required for lethal toxin activity. Mol. Microbiol. 13 (1994) 1093-1100
35. Kocer S.S., Walker S.G., Zerler B., Golub L.M., and Simon S.R. Metalloproteinase inhibitors, nonantimicrobial chemically modified tetracyclines, and ilomastat block Bacillus anthracis lethal factor activity in viable cells. Infect. Immun. 73 (2005) 7548-7557
36. Kochi S.K., Schiavo G., Mock M., and Montecucco C. Zinc content of the Bacillus anthracis lethal factor. FEMS Microbiol. Lett. 124 (1994) 343-348
37. Lacy D., Lin H., Melnyk R., Schueler-Furman O., Reither L., Cunningham K., Baker D., and Collier R. A model of anthrax toxin lethal factor bound to protective antigen. Proc. Natl. Acad. Sci. USA 102 (2005) 16409-16414
38. Lacy D.B., Mourez M., Fouassier A., and Collier R.J. Mapping the anthrax protective antigen binding site on the lethal and edema factors. J. Biol. Chem. 277 (2002) 3006-3010
39. Lee L.V., Bower K.E., Liang F.S., Shi J., Wu D., Sucheck S.J., Vogt P.K., and Wong C.H. Inhibition of the proteolytic activity of anthrax lethal factor by aminoglycosides. J. Am. Chem. Soc. 126 (2004) 4774-4775
40. Leppla S.H. Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells. Proc. Natl. Acad. Sci. USA 79 (1982) 3162-3166
41. Liang X., Young J., Boone S., Waugh D., and Duesbery N. Involvement of domain II in toxicity of anthrax lethal factor. J. Biol. Chem. 279 (2004) 52473-52478
42. Melnyk R.A., and Collier R.J. A loop network within the anthrax toxin pore positions the phenylalanine clamp in an active conformation. Proc. Natl. Acad. Sci. USA 103 (2006) 9802-9807
43. Min D.H., Tang W.J., and Mrksich M. Chemical screening by mass spectrometry to identify inhibitors of anthrax lethal factor. Nat. Biotechnol. 22 (2004) 717-723
44. Mock M., and Roques B. Progress in rapid screening of Bacillus anthracis lethal factor activity. Proc. Natl. Acad. Sci. USA 99 (2002) 6527-6529
45. Mogridge J., Cunningham K., and Collier R.J. The stoichiometry of anthrax toxin complexes. Biochemistry 41 (2002) 1079-1082
46. Montecucco C., Papini E., and Schiavo G. Bacterial protein toxins penetrate cells via a four-step mechanism. FEBS Lett. 346 (1994) 92-98
47. Montecucco C., Tonello F., and Zanotti G. Stop the killer: how to inhibit the anthrax lethal factor metalloprotease. Trends Biochem. Sci. 29 (2004) 282-285
48. Moss J., and Vaughan M. Activation of adenylate cyclase by choleragen. Annu. Rev. Biochem. 48 (1979) 581-600
49. Neumeyer T., Tonello F., Dal Molin F., Schiffler B., and Benz R. Anthrax edema factor, voltage-dependent binding to the protective antigen ion channel and comparison to LF binding. J. Biol. Chem. 281 (2006) 32335-32343
50. Neumeyer T., Tonello F., Dal Molin F., Schiffler B., Orlik F., and Benz R. Anthrax lethal factor (LF) mediated block of the anthrax protective antigen (PA) ion channel: Effect of ionic strength and voltage. Biochemistry 45 (2006) 3060-3068
51. Numa M.M., Lee L.V., Hsu C.C., Bower K.E., and Wong C.H. Identification of novel anthrax lethal factor inhibitors generated by combinatorial Pictet-Spengler reaction followed by screening in situ. ChemBioChem 6 (2005) 1002-1006
52. Panchal R.G., Hermone A.R., Nguyen T.L., Wong T.Y., Schwarzenbacher R., Schmidt J., Lane D., McGrath C., Turk B.E., Burnett J., Aman M.J., Little S., Sausville E.A., Zaharevitz D.W., Cantley L.C., Liddington R.C., Gussio R., and Bavari S. Identification of small molecule inhibitors of anthrax lethal factor. Nat. Struct. Mol. Biol. 11 (2004) 67-72
53. Pannifer A.D., Wong T.Y., Schwarzenbacher R., Renatus M., Petosa C., Bienkowska J., Lacy D.B., Collier R.J., Park S., Leppla S.H., Hanna P., and Liddington R.C. Crystal structure of the anthrax lethal factor. Nature 414 (2001) 229-233
54. Peinado J., Kacprzak M., Leppla S., and Lindberg I. Cross-inhibition between furin and lethal factor inhibitors. Biochem. Biophys. Res. Commun. 321 (2004) 601-605
55. Pettersen E.F., Goddard T.D., Huang C.C., Couch G.S., Greenblatt D.M., Meng E.C., and Ferrin T.E. UCSF chimera - A visualization system for exploratory research and analysis. J. Comput. Chem. 25 (2004) 1605-1612
56. Rainey G.J., and Young J.A. Antitoxins: novel strategies to target agents of bioterrorism. Nat. Rev. Microbiol. 2 (2004) 721-726
57. Rigoni M., Caccin P., Johnson E., Montecucco C., and Rossetto O. Site-directed mutagenesis identifies active-site residues of the light chain of botulinum neurotoxin type A. Biochem. Biophys. Res. Commun. 288 (2001) 1231-1237
58. Rossetto O., Caccin P., Rigoni M., Tonello F., Bortoletto N., Stevens R.C., and Montecucco C. Active-site mutagenesis of tetanus neurotoxin implicates TYR-375 and GLU-271 in metalloproteolytic activity. Toxicon 39 (2001) 1151-1159
59. Rossetto O., Seveso M., Caccin P., Schiavo G., and Montecucco C. Tetanus and botulinum neurotoxins: turning bad guys into good by research. Toxicon 39 (2001) 27-41
60. Schiavo G., Benfenati F., Poulain B., Rossetto O., Polverino de Laureto P., DasGupta B., and Montecucco C. Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin. Nature 359 (1992) 832-835
61. Schiavo G., Rossetto O., Santucci A., DasGupta B.R., and Montecucco C. Botulinum neurotoxins A, B and E are zinc proteins. J. Biol. Chem. 267 (1992) 23479-23483
62. Schiavo G., Poulain B., Rossetto O., Benfenati F., Tauc L., and Montecucco C. Tetanus toxin is a zinc protein and its inhibition of neurotransmitter release depends on zinc. EMBO J. 11 (1992) 3577-3583
63. Shoop W.L., Xiong Y., Wiltsie J., Woods A., Guo J., Pivnichny J.V., Felcetto T., Michael B.F., Bansal A., Cummings R.T., Cunningham B.R., Friedlander A.M., Douglas C.M., Patel S.B., Wisniewski D., Scapin G., Salowe S.P., Zaller D.M., Chapman K.T., Scolnick E.M., Schmatz D.M., Bartizal K., MacCoss M., and Hermes J.D. Anthrax lethal factor inhibition. Proc. Natl. Acad. Sci. USA 102 (2005) 7958-7963
64. Smith H. Discovery of the anthrax toxin: the beginning of studies of virulence determinants regulated in vivo. Int. J. Med. Microbiol. 291 (2002) 411-417
65. Tonello F., Ascenzi P., and Montecucco C. The metalloproteolytic activity of the anthrax lethal factor is substrate-inhibited. J. Biol. Chem. 278 (2003) 40075-40078
66. Tonello F., Naletto L., Romanello V., Dal Molin F., and Montecucco C. Tyrosine-728 and glutamic acid-735 are essential for the metalloproteolytic activity of the lethal factor of Bacillus anthracis. Biochem. Biophys. Res. Commun. 313 (2004) 496-502
67. Tonello F., Schiavo G., and Montecucco C. Metal substitution of tetanus neurotoxin. Biochem. J. 322 (1997) 507-510
68. Tonello F., Seveso M., Marin O., Mock M., and Montecucco C. Screening inhibitors of anthrax lethal factor. Nature 418 (2002) 386
69. Turk B. Discovery and development of anthrax lethal factor metalloproteinase inhibitors. Curr. Pharm. Biotechnol. 9 (2008) 24-33
70. Turk B., Wong T., Schwarzenbacher R., Jarrell E., Leppla S., Collier R., Liddington R., and Cantley L. The structural basis for substrate and inhibitor selectivity of the anthrax lethal factor. Nat. Struct. Mol. Biol. 11 (2004) 60-66
71. Vitale G., Bernardi L., Napolitani G., Mock M., and Montecucco C. Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor. Biochem. J. 352 (2000) 739-745
72. Vitale G., Pellizzari R., Recchi C., Napolitani G., Mock M., and 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. 248 (1998) 706-711
73. Wickliffe K.E., Leppla S.H., and Moayeri M. Killing of macrophages by anthrax lethal toxin: involvement of the N-end rule pathway. Cell. Microbiol. 10 (2008) 1352-1362
74. Zakharova M., Kuznetcov N., Dubiley S., Kozyr A., Fedorova O., Chudakov D., Knorre D., Shemyakin I., Gabibov A., and Kolesnikov A. Substrate recognition of anthrax lethal factor examined by combinatorial and pre-steady-state kinetic approaches. J. Biol. Chem. 284 (2009) 17902-17913
75. Zhang S., Finkelstein A., and Collier R.J. Evidence that translocation of anthrax toxin's lethal factor is initiated by entry of its N terminus into the protective antigen channel. Proc. Natl. Acad. Sci. USA 101 (2004) 16756-16761
76. Xiong Y., Wiltsie J., Woods A., Guo J., Pivnichny J.V., Tang W., Bansal A., Cummings R.T., Cunningham B.R., Friedlander A.M., Douglas C.M., Salowe S.P., Zaller D.M., Scolnick E.M., Schmatz D.M., Bartizal K., Hermes J.D., MacCoss M., and Chapman K.T. The discovery of a potent and selective lethal factor inhibitor for adjunct therapy of anthrax infection. Bioorg. Med. Chem. Lett. 16 (2006) 964-968