Skip to main content
SpringerLink
Log in

Exceptionally Selective Substrate Targeting by the Metalloprotease Anthrax Lethal Factor

  • Chapter
  • First Online:
Protein Reviews – Purinergic Receptors

Part of the book series: Advances in Experimental Medicine and Biology ((PROTRE,volume 1111))

Abstract

The zinc-dependent metalloprotease anthrax lethal factor (LF) is the enzymatic component of a toxin thought to have a major role in Bacillus anthracis infections. Like many bacterial toxins, LF is a secreted protein that functions within host cells. LF is a highly selective protease that cleaves a limited number of substrates in a site-specific manner, thereby impacting host signal transduction pathways. The major substrates of LF are mitogen-activated protein kinase kinases (MKKs), which lie in the middle of three-component phosphorylation cascades mediating numerous functions in a variety of cells and tissues. How LF targets its limited substrate repertoire has been an active area of investigation. LF recognizes a specific sequence motif surrounding the scissile bonds of substrate proteins. X-ray crystallography of the protease in complex with peptide substrates has revealed the structural basis of selectivity for the LF cleavage site motif. In addition to having interactions proximal to the cleavage site, LF binds directly to a more distal region in its substrates through a so-called exosite interaction. This exosite has been mapped to a surface within a non-catalytic domain of LF with previously unknown function. A putative LF-binding site has likewise been identified on the catalytic domains of MKKs. Here we review our current state of understanding of LF-substrate interactions and discuss the implications for the design and discovery of inhibitors that may have utility as anthrax therapeutics.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

AC:

Adenylyl cyclase

BoNT:

Botulinum neurotoxin

cAMP:

Cyclic AMP

EdTx:

Edema toxin

EF:

Edema factor

HTS:

High-throughput screening

LeTx:

Lethal toxin

LF:

Anthrax lethal factor

MAPK:

Mitogen-activated protein kinase

MKK:

Mitogen-activated protein kinase kinase

NLRP:

NACHT domain, leucine rich repeat and pyrin domain containing protein

NOS1:

Constitutive nitric oxide synthase

PA:

Protective antigen

PAMP:

Pathogen-associated molecular pattern

References

  • Abrami L, Reig N, van der Goot FG (2005) Anthrax toxin: the long and winding road that leads to the kill. Trends Microbiol 13(2):72–78

    CAS  PubMed  Google Scholar 

  • Agrawal A, Lingappa J, Leppla SH, Agrawal S, Jabbar A, Quinn C, Pulendran B (2003) Impairment of dendritic cells and adaptive immunity by anthrax lethal toxin. Nature 424(6946):329–334

    CAS  PubMed  Google Scholar 

  • Arora N, Leppla SH (1993) Residues 1-254 of anthrax toxin lethal factor are sufficient to cause cellular uptake of fused polypeptides. J Biol Chem 268(5):3334–3341

    CAS  PubMed  Google Scholar 

  • Atwal JK, Chen Y, Chiu C, Mortensen DL, Meilandt WJ, Liu Y, Heise CE, Hoyte K, Luk W, Lu Y, Peng K, Wu P, Rouge L, Zhang Y, Lazarus RA, Scearce-Levie K, Wang W, Wu Y, Tessier-Lavigne M, Watts RJ (2011) A therapeutic antibody targeting BACE1 inhibits amyloid-beta production in vivo. Sci Transl Med 3(84):84ra43

    PubMed  Google Scholar 

  • Baldari CT, Tonello F, Paccani SR, Montecucco C (2006) Anthrax toxins: a paradigm of bacterial immune suppression. Trends Immunol 27(9):434–440

    CAS  PubMed  Google Scholar 

  • Bannwarth L, Goldberg AB, Chen C, Turk BE (2012) Identification of exosite-targeting inhibitors of anthrax lethal factor by high-throughput screening. Chem Biol 19(7):875–882

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bardwell AJ, Abdollahi M, Bardwell L (2004) Anthrax lethal factor-cleavage products of MAPK (mitogen-activated protein kinase) kinases exhibit reduced binding to their cognate MAPKs. Biochem J 378(Pt 2):569–577

    CAS  PubMed  PubMed Central  Google Scholar 

  • Biondi RM, Nebreda AR (2003) Signalling specificity of Ser/Thr protein kinases through docking-site-mediated interactions. Biochem J 372 .(Pt 1:1–13

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bjorklund M, Heikkila P, Koivunen E (2004) Peptide inhibition of catalytic and noncatalytic activities of matrix metalloproteinase-9 blocks tumor cell migration and invasion. J Biol Chem 279(28):29589–29597

    PubMed  Google Scholar 

  • Boyden ED, Dietrich WF (2006) Nalp1b controls mouse macrophage susceptibility to anthrax lethal toxin. Nat Genet 38(2):240–244

    CAS  PubMed  Google Scholar 

  • Cafardi V, Biagini M, Martinelli M, Leuzzi R, Rubino JT, Cantini F, Norais N, Scarselli M, Serruto D, Unnikrishnan M (2013) Identification of a novel zinc metalloprotease through a global analysis of Clostridium difficile extracellular proteins. PLoS One 8(11):e81306

    PubMed  PubMed Central  Google Scholar 

  • Cerda-Costa N, Gomis-Ruth FX (2014) Architecture and function of metallopeptidase catalytic domains. Protein Sci 23(2):123–144

    CAS  PubMed  Google Scholar 

  • Chavarria-Smith J, Vance RE (2013) Direct proteolytic cleavage of NLRP1B is necessary and sufficient for inflammasome activation by anthrax lethal factor. PLoS Pathog 9(6):e1003452

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chavarria-Smith J, Mitchell PS, Ho AM, Daugherty MD, Vance RE (2016) Functional and evolutionary analyses identify proteolysis as a general mechanism for NLRP1 inflammasome activation. PLoS Pathog 12(12):e1006052

    PubMed  PubMed Central  Google Scholar 

  • Chopra AP, Boone SA, Liang X, Duesbery NS (2003) Anthrax lethal factor proteolysis and inactivation of MAPK kinase. J Biol Chem 278(11):9402–9406

    CAS  PubMed  Google Scholar 

  • Crawford MA, Aylott CV, Bourdeau RW, Bokoch GM (2006) Bacillus anthracis toxins inhibit human neutrophil NADPH oxidase activity. J Immunol 176(12):7557–7565

    CAS  PubMed  Google Scholar 

  • Cybulski RJ Jr, Sanz P, O'Brien AD (2009) Anthrax vaccination strategies. Mol Asp Med 30(6):490–502

    CAS  Google Scholar 

  • Dennis MS, Eigenbrot C, Skelton NJ, Ultsch MH, Santell L, Dwyer MA, O’Connell MP, Lazarus RA (2000) Peptide exosite inhibitors of factor VIIa as anticoagulants. Nature 404(6777):465–470

    CAS  PubMed  Google Scholar 

  • Duesbery NS, Webb CP, Leppla SH, Gordon VM, Klimpel KR, Copeland TD, Ahn NG, Oskarsson MK, Fukasawa K, Paull KD, Vande Woude GF (1998) Proteolytic inactivation of MAP-kinase-kinase by anthrax lethal factor. Science 280(5364):734–737

    CAS  PubMed  Google Scholar 

  • During RL, Li W, Hao B, Koenig JM, Stephens DS, Quinn CP, Southwick FS (2005) Anthrax lethal toxin paralyzes neutrophil actin-based motility. J Infect Dis 192(5):837–845

    CAS  PubMed  Google Scholar 

  • Fink SL, Bergsbaken T, Cookson BT (2008) Anthrax lethal toxin and Salmonella elicit the common cell death pathway of caspase-1-dependent pyroptosis via distinct mechanisms. Proc Natl Acad Sci U S A 105(11):4312–4317

    CAS  PubMed  PubMed Central  Google Scholar 

  • Firoved AM, Miller GF, Moayeri M, Kakkar R, Shen Y, Wiggins JF, McNally EM, Tang WJ, Leppla SH (2005) Bacillus anthracis edema toxin causes extensive tissue lesions and rapid lethality in mice. Am J Pathol 167(5):1309–1320

    CAS  PubMed  PubMed Central  Google Scholar 

  • Friedlander AM (1986) Macrophages are sensitive to anthrax lethal toxin through an acid-dependent process. J Biol Chem 261(16):7123–7126

    CAS  PubMed  Google Scholar 

  • Goldberg AB, Turk BE (2016) Inhibitors of the metalloproteinase anthrax lethal factor. Curr Top Med Chem 16(21):2350–2358

    CAS  PubMed  PubMed Central  Google Scholar 

  • Goldberg AB, Cho E, Miller CJ, Lou HJ, Turk BE (2017) Identification of a substrate-selective exosite within the metalloproteinase anthrax lethal factor. J Biol Chem 292(3):814–825

    CAS  PubMed  Google Scholar 

  • Grubbs KJ, Bleich RM, Santa Maria KC, Allen SE, Farag S, AgBiome T, Shank EA, Bowers AA (2017) Large-scale bioinformatics analysis of Bacillus genomes uncovers conserved roles of natural products in bacterial physiology. mSystems 2(6):e00040

    CAS  PubMed  PubMed Central  Google Scholar 

  • Haling JR, Sudhamsu J, Yen I, Sideris S, Sandoval W, Phung W, Bravo BJ, Giannetti AM, Peck A, Masselot A, Morales T, Smith D, Brandhuber BJ, Hymowitz SG, Malek S (2014) Structure of the BRAF-MEK complex reveals a kinase activity independent role for BRAF in MAPK signaling. Cancer Cell 26(3):402–413

    CAS  PubMed  Google Scholar 

  • Hellmich KA, Levinsohn JL, Fattah R, Newman ZL, Maier N, Sastalla I, Liu S, Leppla SH, Moayeri M (2012) Anthrax lethal factor cleaves mouse Nlrp1b in both toxin-sensitive and toxin-resistant macrophages. PLoS One 7(11):e49741

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jiao GS, Kim S, Moayeri M, Cregar-Hernandez L, McKasson L, Margosiak SA, Leppla SH, Johnson AT (2010) Antidotes to anthrax lethal factor intoxication. Part 1: discovery of potent lethal factor inhibitors with in vivo efficacy. Bioorg Med Chem Lett 20(22):6850–6853

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jiao GS, Kim S, Moayeri M, Crown D, Thai A, Cregar-Hernandez L, McKasson L, Sankaran B, Lehrer A, Wong T, Johns L, Margosiak SA, Leppla SH, Johnson AT (2012) Antidotes to anthrax lethal factor intoxication. Part 3: evaluation of core structures and further modifications to the C2-side chain. Bioorg Med Chem Lett 22(6):2242–2246

    CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson GL, Lapadat R (2002) Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298(5600):1911–1912

    CAS  PubMed  Google Scholar 

  • Julien O, Wells JA (2017) Caspases and their substrates. Cell Death Differ 24(8):1380–1389

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kandadi MR, Hua Y, Ma H, Li Q, Kuo SR, Frankel AE, Ren J (2010) Anthrax lethal toxin suppresses murine cardiomyocyte contractile function and intracellular Ca2+ handling via a NADPH oxidase-dependent mechanism. PLoS One 5(10):e13335

    PubMed  PubMed Central  Google Scholar 

  • Kim J, Park H, Myung-Hyun J, Han SH, Chung H, Lee JS, Park JS, Yoon MY (2008) The effects of anthrax lethal factor on the macrophage proteome: potential activity on nitric oxide synthases. Arch Biochem Biophys 472(1):58–64

    CAS  PubMed  Google Scholar 

  • Kim S, Jiao GS, Moayeri M, Crown D, Cregar-Hernandez L, McKasson L, Margosiak SA, Leppla SH, Johnson AT (2011) Antidotes to anthrax lethal factor intoxication. Part 2: structural modifications leading to improved in vivo efficacy. Bioorg Med Chem Lett 21(7):2030–2033

    CAS  PubMed  PubMed Central  Google Scholar 

  • Klein F, Hodges DR, Mahlandt BG, Jones WI, Haines BW, Lincoln RE (1962) Anthrax toxin: causative agent in the death of rhesus monkeys. Science 138:1331–1333

    CAS  PubMed  Google Scholar 

  • Krachler AM, Woolery AR, Orth K (2011) Manipulation of kinase signaling by bacterial pathogens. J Cell Biol 195(7):1083–1092

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lee CS, Dykema KJ, Hawkins DM, Cherba DM, Webb CP, Furge KA, Duesbery NS (2011) MEK2 is sufficient but not necessary for proliferation and anchorage-independent growth of SK-MEL-28 melanoma cells. PLoS One 6(2):e17165

    CAS  PubMed  PubMed Central  Google Scholar 

  • Levinsohn JL, Newman ZL, Hellmich KA, Fattah R, Getz MA, Liu S, Sastalla I, Leppla SH, Moayeri M (2012) Anthrax lethal factor cleavage of Nlrp1 is required for activation of the inflammasome. PLoS Pathog 8(3):e1002638

    PubMed  PubMed Central  Google Scholar 

  • Li H, Xu H, Zhou Y, Zhang J, Long C, Li S, Chen S, Zhou JM, Shao F (2007) The phosphothreonine lyase activity of a bacterial type III effector family. Science 315(5814):1000–1003

    CAS  PubMed  Google Scholar 

  • Li F, Terzyan S, Tang J (2011) Subsite specificity of anthrax lethal factor and its implications for inhibitor development. Biochem Biophys Res Commun 407(2):400–405

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liang X, Young JJ, Boone SA, Waugh DS, Duesbery NS (2004) Involvement of domain II in toxicity of anthrax lethal factor. J Biol Chem 279(50):52473–52478

    CAS  PubMed  Google Scholar 

  • Liu S, Crown D, Miller-Randolph S, Moayeri M, Wang H, Hu H, Morley T, Leppla SH (2009) Capillary morphogenesis protein-2 is the major receptor mediating lethality of anthrax toxin in vivo. Proc Natl Acad Sci U S A 106(30):12424–12429

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu S, Miller-Randolph S, Crown D, Moayeri M, Sastalla I, Okugawa S, Leppla SH (2010) Anthrax toxin targeting of myeloid cells through the CMG2 receptor is essential for establishment of Bacillus anthracis infections in mice. Cell Host Microbe 8(5):455–462

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu S, Zhang Y, Moayeri M, Liu J, Crown D, Fattah RJ, Wein AN, Yu ZX, Finkel T, Leppla SH (2013) Key tissue targets responsible for anthrax-toxin-induced lethality. Nature 501(7465):63–68

    CAS  PubMed  PubMed Central  Google Scholar 

  • Maize KM, Kurbanov EK, De L, Mora-Rey T, Geders TW, Hwang DJ, Walters MA, Johnson RL, Amin EA, Finzel BC (2014) Anthrax toxin lethal factor domain 3 is highly mobile and responsive to ligand binding. Acta Crystallogr D Biol Crystallogr 70. (Pt 11:2813–2822

    CAS  PubMed  PubMed Central  Google Scholar 

  • Maize KM, Kurbanov EK, Johnson RL, Amin EA, Finzel BC (2015) Ligand-induced expansion of the S1' site in the anthrax toxin lethal factor. FEBS Lett 589(24 Pt B):3836–3841

    CAS  PubMed  PubMed Central  Google Scholar 

  • Moayeri M, Leppla SH (2009) Cellular and systemic effects of anthrax lethal toxin and edema toxin. Mol Asp Med 30(6):439–455

    CAS  Google Scholar 

  • Moayeri M, Martinez NW, Wiggins J, Young HA, Leppla SH (2004) Mouse susceptibility to anthrax lethal toxin is influenced by genetic factors in addition to those controlling macrophage sensitivity. Infect Immun 72(8):4439–4447

    CAS  PubMed  PubMed Central  Google Scholar 

  • Moayeri M, Crown D, Dorward DW, Gardner D, Ward JM, Li Y, Cui X, Eichacker P, Leppla SH (2009) The heart is an early target of anthrax lethal toxin in mice: a protective role for neuronal nitric oxide synthase (nNOS). PLoS Pathog 5(5):e1000456

    PubMed  PubMed Central  Google Scholar 

  • Mock M, Fouet A (2001) Anthrax. Annu Rev Microbiol 55:647–671

    CAS  PubMed  Google Scholar 

  • Mohamed N, Clagett M, Li J, Jones S, Pincus S, D'Alia G, Nardone L, Babin M, Spitalny G, Casey L (2005) A high-affinity monoclonal antibody to anthrax protective antigen passively protects rabbits before and after aerosolized Bacillus anthracis spore challenge. Infect Immun 73(2):795–802

    CAS  PubMed  PubMed Central  Google Scholar 

  • Newman ZL, Printz MP, Liu S, Crown D, Breen L, Miller-Randolph S, Flodman P, Leppla SH, Moayeri M (2010) Susceptibility to anthrax lethal toxin-induced rat death is controlled by a single chromosome 10 locus that includes rNlrp1. PLoS Pathog 6(5):e1000906

    PubMed  PubMed Central  Google Scholar 

  • Ngai S, Batty S, Liao KC, Mogridge J (2010) An anthrax lethal factor mutant that is defective at causing pyroptosis retains proapoptotic activity. FEBS J 277(1):119–127

    CAS  PubMed  Google Scholar 

  • O'Brien J, Friedlander A, Dreier T, Ezzell J, Leppla S (1985) Effects of anthrax toxin components on human neutrophils. Infect Immun 47(1):306–310

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pannifer AD, Wong TY, Schwarzenbacher R, Renatus M, Petosa C, Bienkowska J, Lacy DB, Collier RJ, Park S, Leppla SH, Hanna P, Liddington RC (2001) Crystal structure of the anthrax lethal factor. Nature 414(6860):229–233

    CAS  PubMed  Google Scholar 

  • Paton AW, Beddoe T, Thorpe CM, Whisstock JC, Wilce MC, Rossjohn J, Talbot UM, Paton JC (2006) AB5 subtilase cytotoxin inactivates the endoplasmic reticulum chaperone BiP. Nature 443(7111):548–552

    CAS  PubMed  Google Scholar 

  • Pezard C, Berche P, Mock M (1991) Contribution of individual toxin components to virulence of Bacillus anthracis. Infect Immun 59(10):3472–3477

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pirazzini M, Rossetto O, Eleopra R, Montecucco C (2017) Botulinum neurotoxins: biology, pharmacology, and toxicology. Pharmacol Rev 69(2):200–235

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rawlings ND, Barrett AJ, Thomas PD, Huang X, Bateman A, Finn RD (2018) The MEROPS database of proteolytic enzymes, their substrates and inhibitors in 2017 and a comparison with peptidases in the PANTHER database. Nucleic Acids Res 46(D1):D624–D632

    CAS  PubMed  Google Scholar 

  • Schacherl M, Pichlo C, Neundorf I, Baumann U (2015) Structural basis of proline-proline peptide bond specificity of the metalloprotease Zmp1 implicated in motility of Clostridium difficile. Structure 23(9):1632–1642

    CAS  PubMed  Google Scholar 

  • Shoop WL, Xiong Y, Wiltsie J, Woods A, Guo J, Pivnichny JV, Felcetto T, Michael BF, Bansal A, Cummings RT, Cunningham BR, Friedlander AM, Douglas CM, Patel SB, Wisniewski D, Scapin G, Salowe SP, Zaller DM, Chapman KT, Scolnick EM, Schmatz DM, Bartizal K, MacCoss M, Hermes JD (2005) Anthrax lethal factor inhibition. Proc Natl Acad Sci U S A 102(22):7958–7963

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sullivan M, Hornig NC, Porstmann T, Uhlmann F (2004) Studies on substrate recognition by the budding yeast separase. J Biol Chem 279(2):1191–1196

    CAS  PubMed  Google Scholar 

  • Tang WJ, Guo Q (2009) The adenylyl cyclase activity of anthrax edema factor. Mol Asp Med 30(6):423–430

    CAS  Google Scholar 

  • Thomas G (2002) Furin at the cutting edge: from protein traffic to embryogenesis and disease. Nat Rev Mol Cell Biol 3(10):753–766

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tonello F, Seveso M, Marin O, Mock M, Montecucco C (2002) Screening inhibitors of anthrax lethal factor. Nature 418(6896):386

    CAS  PubMed  Google Scholar 

  • Tonello F, Naletto L, Romanello V, Dal Molin F, Montecucco C (2004) Tyrosine-728 and glutamic acid-735 are essential for the metalloproteolytic activity of the lethal factor of Bacillus anthracis. Biochem Biophys Res Commun 313(3):496–502

    CAS  PubMed  Google Scholar 

  • Tournier JN, Quesnel-Hellmann A, Mathieu J, Montecucco C, Tang WJ, Mock M, Vidal DR, Goossens PL (2005) Anthrax edema toxin cooperates with lethal toxin to impair cytokine secretion during infection of dendritic cells. J Immunol 174(8):4934–4941

    CAS  PubMed  Google Scholar 

  • Tschopp J, Martinon F, Burns K (2003) NALPs: a novel protein family involved in inflammation. Nat Rev Mol Cell Biol 4(2):95–104

    CAS  PubMed  Google Scholar 

  • Turk B (2006) Targeting proteases: successes, failures and future prospects. Nat Rev Drug Discov 5(9):785–799

    CAS  PubMed  Google Scholar 

  • Turk BE (2007) Manipulation of host signalling pathways by anthrax toxins. Biochem J 402(3):405–417

    CAS  PubMed  Google Scholar 

  • Turk BE, Wong TY, Schwarzenbacher R, Jarrell ET, Leppla SH, Collier RJ, Liddington RC, Cantley LC (2004) The structural basis for substrate and inhibitor selectivity of the anthrax lethal factor. Nat Struct Mol Biol 11(1):60–66

    CAS  PubMed  Google Scholar 

  • Tyndall JDA, Nall T, Fairlie DP (2005) Proteases universally recognize beta strands in their active sites. Chem Rev 105(3):973–999

    CAS  PubMed  Google Scholar 

  • Vitale G, Pellizzari R, Recchi C, Napolitani G, Mock M, Montecucco C (1998) Anthrax lethal factor cleaves the N-terminus of MAPKKs and induces tyrosine/threonine phosphorylation of MAPKs in cultured macrophages. Biochem Biophys Res Commun 248(3):706–711

    CAS  PubMed  Google Scholar 

  • Vitale G, Bernardi L, Napolitani G, Mock M, Montecucco C (2000) Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor. Biochem J 352(Pt 3):739–745

    CAS  PubMed  PubMed Central  Google Scholar 

  • Watters JW, Dietrich WF (2001) Genetic, physical, and transcript map of the Ltxs1 region of mouse chromosome 11. Genomics 73(2):223–231

    CAS  PubMed  Google Scholar 

  • Welkos SL, Keener TJ, Gibbs PH (1986) Differences in susceptibility of inbred mice to Bacillus anthracis. Infect Immun 51(3):795–800

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wright GG, Mandell GL (1986) Anthrax toxin blocks priming of neutrophils by lipopolysaccharide and by muramyl dipeptide. J Exp Med 164(5):1700–1709

    CAS  PubMed  Google Scholar 

  • Wu S, Lim KC, Huang J, Saidi RF, Sears CL (1998) Bacteroides fragilis enterotoxin cleaves the zonula adherens protein, E-cadherin. Proc Natl Acad Sci U S A 95(25):14979–14984

    CAS  PubMed  PubMed Central  Google Scholar 

  • Xu Q, Gohler AK, Kosfeld A, Carlton D, Chiu HJ, Klock HE, Knuth MW, Miller MD, Elsliger MA, Deacon AM, Godzik A, Lesley SA, Jahreis K, Wilson IA (2012) The structure of Mlc titration factor A (MtfA/YeeI) reveals a prototypical zinc metallopeptidase related to anthrax lethal factor. J Bacteriol 194(11):2987–2999

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zakharova MY, Kuznetsov NA, Dubiley SA, Kozyr AV, Fedorova OS, Chudakov DM, Knorre DG, Shemyakin IG, Gabibov AG, Kolesnikov AV (2009) Substrate recognition of anthrax lethal factor examined by combinatorial and pre-steady-state kinetic approaches. J Biol Chem 284(27):17902–17913

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by National Institutes of Health grant R01 GM104047.

Conflicts of Interest

The author declares no conflict of interests.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Yale School of Medicine, New Haven, CT, USA

    Benjamin E. Turk

Authors
  1. Benjamin E. Turk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Benjamin E. Turk .

Editor information

Editors and Affiliations

  1. Biochem and Mol Biol, Baylor College of Medicine, Houston, TX, USA

    M. Zouhair Atassi

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Turk, B.E. (2018). Exceptionally Selective Substrate Targeting by the Metalloprotease Anthrax Lethal Factor. In: Atassi, M. (eds) Protein Reviews – Purinergic Receptors. Advances in Experimental Medicine and Biology(), vol 1111. Springer, Cham. https://doi.org/10.1007/5584_2018_273

Download citation

Publish with us

Policies and ethics

Search

Navigation