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The FEBS Journal

Cover image for Vol. 278 Issue 23

Special Issue: Engineering Toxins for 21st Century Therapies

December 2011

Volume 278, Issue 23

Pages 4453–4701

  1. Special Issue

    1. Top of page
    2. Special Issue
    3. Author Index
    1. You have free access to this content
      Special Issue: Engineering toxins for 21st-century therapies : Introduction (page 4453)

      K. Ravi Acharya

      Version of Record online: 3 NOV 2011 | DOI: 10.1111/j.1742-4658.2011.08384.x

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      This special issue on ‘Engineering toxins for 21st century therapies’ provides a critical review of the current state of multifaceted aspects of toxin research by some of the leading researchers in the field. It also highlights the clinical potential and challenges for development of novel biologics based on engineered toxin derived products

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      Novel therapeutics based on recombinant botulinum neurotoxins to normalize the release of transmitters and pain mediators (pages 4454–4466)

      J. Oliver Dolly, Jiafu Wang, Tomas H. Zurawski and Jianghui Meng

      Version of Record online: 5 JUL 2011 | DOI: 10.1111/j.1742-4658.2011.08205.x

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      A major unmet clinical need exists for long-acting neurotherapeutics to alleviate chronic pain in patients unresponsive to available non-addictive analgesics. This review describes a recombinant strategy for engineering new generations of botulinum neurotoxin-based therapeutics for attenuating transmitter release from pain-sensing neurons. Combining identified advantageous features from two serotypes yielded a novel, long-lasting and synergistically acting biotherapeutic with antinociceptive potential

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      Molecular structures and functional relationships in clostridial neurotoxins (pages 4467–4485)

      Subramanyam Swaminathan

      Version of Record online: 13 JUN 2011 | DOI: 10.1111/j.1742-4658.2011.08183.x

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      Clostridium botulinum neurotoxins are the most potent toxins known. They cause botulism, a deadly disease in humans and animals, and are both public health hazard and potential biowarfare agent. Botulinum neurotoxin consists of multiple domains, each domain being responsible for a specific function in its toxicity. This review describes their molecular structures and discusses the structure-function relation of each domain

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      Unique ganglioside binding by botulinum neurotoxins C and D-SA (pages 4486–4496)

      Abby R. Kroken, Andrew P.-A. Karalewitz, Zhuji Fu, Michael R. Baldwin, Jung-Ja P. Kim and Joseph T. Barbieri

      Version of Record online: 31 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08166.x

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      There are seven botulinum neurotoxins (BoNTS) serotypes (A-G). BoNT/C and BoNT/D serotypes include mosaic toxins that are organized as D-C and C-D toxins. BoNT/C, BoNT/D, and BoNT/D-SA lack components of the ganglioside binding pocket that exist within other BoNT serotypes, but possess a unique ganglioside binding loop. Defining how BoNTs enter host cells provides insight towards extending BoNT therapys

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      Vesicular traffic in cell navigation (pages 4497–4505)

      Kathleen Zylbersztejn and Thierry Galli

      Version of Record online: 31 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08168.x

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      Cell navigation is the process whereby cells or cytoplasmic extensions are guided from one point to another in multicellular organisms. Here we review the important functions of several v- and t-SNAREs proteins, necessary for membrane fusion, in migration, axon growth and guidance. We conclude that endosomal SNAREs are important for cell navigation, opening avenues for fundamental research and therapeutic applications

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      Exchange of the HCC domain mediating double receptor recognition improves the pharmacodynamic properties of botulinum neurotoxin (pages 4506–4515)

      Andreas Rummel, Stefan Mahrhold, Hans Bigalke and Thomas Binz

      Version of Record online: 22 JUN 2011 | DOI: 10.1111/j.1742-4658.2011.08196.x

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      The high structural homology of botulinum neurotoxin serotypes paves the way to exchange domains to alter pharmacodynamic characteristics of BoNTs without impairing structural integrity e.g.: the exchange of the HCC domain exhibiting the ganglioside and protein receptor binding sites in BoNT/A yielded a hybrid neurotoxin with increased receptor binding affinity and potency which leads towards an improved peripheral muscle relaxant

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      Solution and membrane-bound chaperone activity of the diphtheria toxin translocation domain towards the catalytic domain (pages 4516–4525)

      Anne Chassaing, Sylvain Pichard, Anne Araye-Guet, Julien Barbier, Vincent Forge and Daniel Gillet

      Version of Record online: 9 MAR 2011 | DOI: 10.1111/j.1742-4658.2011.08053.x

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      The translocation (T) domain of diphtheria toxin acts as a specialized pH-dependent chaperone for the catalytic (C) domain of the toxin during the initial steps of translocation. T stabilizes the partially folded states of C corresponding to each step of the process. Interestingly, this chaperone activity acts on very different states of C ie: in solution, membrane-bound and membrane inserted

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      Actin as target for modification by bacterial protein toxins (pages 4526–4543)

      Klaus Aktories, Alexander E. Lang, Carsten Schwan and Hans G. Mannherz

      Version of Record online: 4 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08113.x

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      Various bacterial protein toxins and effectors target the actin cytoskeleton. Binary actin-ADP-ribosylating exotoxins cause ADP-ribosylation of actin at Arg177, thereby inhibiting actin polymerization. Photorhabdus luminescens toxin complex that ADP-ribosylates actin at Thr148, promotes actin polymerization and forms actin aggregates. A third group of bacterial toxins/effectors (e.g. Vibrio cholerae RTX toxin) catalyses a chemical cross-linking reaction of actin thereby forming oligomers, while blocking the polymerization of actin to functional filaments

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      Enzymatic toxins from snake venom: structural characterization and mechanism of catalysis (pages 4544–4576)

      Tse Siang Kang, Dessislava Georgieva, Nikolay Genov, Mário T. Murakami, Mau Sinha, Ramasamy P. Kumar, Punit Kaur, Sanjit Kumar, Sharmistha Dey, Sujata Sharma, Alice Vrielink, Christian Betzel, Soichi Takeda, Raghuvir K. Arni, Tej P. Singh and R. Manjunatha Kini

      Version of Record online: 17 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08115.x

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      Snake venoms are cocktails of enzymes and non-enzymatic proteins. Here, we describe the structures of the common snake venom enzymes, namely, acetylcholinesterase, L-amino acid oxidase, phospholipase A2, serine proteinase, and metalloproteinase, and their complexes. We discuss the contribution of these structures in understanding the mechanisms of catalysis and inhibition as well as in the structure-based design of new, potent inhibitors

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      Do bacterial genotoxins contribute to chronic inflammation, genomic instability and tumor progression? (pages 4577–4588)

      Lina Guerra, Riccardo Guidi and Teresa Frisan

      Version of Record online: 17 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08125.x

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      The cytolethal distending toxin, produced by Gram negative bacteria, and colibactin, secreted by commensal and extraintestinal pathogenic Escherichia coli strains, are the first bacterial toxins known to cause DNA damage in eukaryotic cells. We reviewed the cellular responses induced by these toxins, focusing on how prolonged intoxication may lead to chronic inflammation, accumulation of genomic instability, and tumor progression

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      Molecular basis of toxicity of Clostridium perfringens epsilon toxin (pages 4589–4601)

      Monika Bokori-Brown, Christos G. Savva, Sérgio P. Fernandes da Costa, Claire E. Naylor, Ajit K. Basak and Richard W. Titball

      Version of Record online: 19 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08140.x

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      Clostridium perfringensε-toxin is the etiologic agent of enterotoxaemia and appears to target the brain and kidneys. The crystal structure of ε-toxin reveals similarity to aerolysin from Aeromonas hydrophila, parasporin-2 from Bacillus thuringiensis, and a lectin from Laetiporus sulphurous. Like these toxins, ε-toxin forms pores in target cell membranes, but differs from these toxins because of its high specificity and potency

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      Epsilon toxin: a fascinating pore-forming toxin (pages 4602–4615)

      Michel R. Popoff

      Version of Record online: 25 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08145.x

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      Clostridium perfringensε-toxin is a potent lethal toxin, which is responsible for animal enterotoxemia. It is structurally related to aerolysin and Clostridium septicumα-toxin. These toxins heptamerize, form pores through the plasma membrane, and induce cell necrosis, ε-toxin being the most potent. ε-toxin accumulates in the kidneys, passes the blood brain barrier and stimulates the glutamate release

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      Cellular and molecular action of the mitogenic protein-deamidating toxin from Pasteurella multocida (pages 4616–4632)

      Brenda A. Wilson and Mengfei Ho

      Version of Record online: 31 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08158.x

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      Pasteurella multocida toxin (PMT), a member of the dermonecrotic toxin family that includes toxins from Bordetella, Escherichia coli and Yersinia, stimulates host cell mitogenic and survival pathways, while inhibiting pathways involved in cellular differentiation. Structural and biochemical studies demonstrate that PMT modulates these signaling pathways through deamidation of a critical active site glutamine residue in its heterotrimeric G-protein targets

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      Membrane interaction of Pasteurella multocida toxin involves sphingomyelin (pages 4633–4648)

      Michael C. Brothers, Mengfei Ho, Ram Maharjan, Nathan C. Clemons, Yuka Bannai, Mark A. Waites, Melinda J. Faulkner, Theresa B. Kuhlenschmidt, Mark S. Kuhlenschmidt, Steven R. Blanke, Chad M. Rienstra and Brenda A. Wilson

      Version of Record online: 20 OCT 2011 | DOI: 10.1111/j.1742-4658.2011.08365.x

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      Pasteurella multocida toxin (PMT) binds preferentially to phosphatidylcholine and sphingomyelin developed on TLC plates, incorporated into liposomes, or loaded onto BiaCore L1 chips. Surface plasmon resonance analysis of PMT binding to ghosts from HEK-293T cells treated with phospholipase D, sphingomyelinase, or trypsin suggests interplay among phosphatidylcholine, sphingomyelin and protein coreceptors in the cellular binding of PMT

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      Gram-positive bacterial superantigen outside-in signaling causes toxic shock syndrome (pages 4649–4667)

      Amanda J. Brosnahan and Patrick M. Schlievert

      Version of Record online: 19 MAY 2011 | DOI: 10.1111/j.1742-4658.2011.08151.x

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      Superantigens, made by the Gram-positive pathogens Staphylococcus aureus and Streptococcus pyogenes, induce a massive cytokine cascade through their interactions with T cells and antigen presenting cells to cause toxic shock syndrome. In this review we cover the additional ability of superantigens to induce proinflammatory cytokines and chemokines from epithelial cells as a way to initiate disease from mucosal surfaces

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      The ins and outs of pertussis toxin (pages 4668–4682)

      Camille Locht, Loic Coutte and Nathalie Mielcarek

      Version of Record online: 4 AUG 2011 | DOI: 10.1111/j.1742-4658.2011.08237.x

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      Pertussis toxin is a major virulence factor of Bordetella pertussis, the etiological agent of whooping cough, and also one of the main antigens in all current pertussis vaccines. It is one of the most complex bacterial toxins, composed of five different subunits and organized in an A-B structure, in which the A protomer expresses ADPribosyltransferase activity and the B oligomer is responsible for toxin binding to the target cell receptors. After binding the toxin traffics via a retrograde transport to the target substrate. As a fully assembled protein it is secreted through the bacterial cell wall by a type IV secretion system

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      A guide to taming a toxin – recombinant immunotoxins constructed from Pseudomonas exotoxin A for the treatment of cancer (pages 4683–4700)

      John E. Weldon and Ira Pastan

      Version of Record online: 2 JUN 2011 | DOI: 10.1111/j.1742-4658.2011.08182.x

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      The modular structure and corresponding mechanism of action of Pseudomonas exotoxin A (PE) are amenable to extensive modifications that can redirect the potent cytotoxicity of this virulence factor toward a therapeutic purpose. This review summarizes our current understanding of PE, its intoxication pathway, and ongoing efforts to convert this toxin into a treatment for cancer

  2. Author Index

    1. Top of page
    2. Special Issue
    3. Author Index
    1. You have free access to this content
      Author index (page 4701)

      Version of Record online: 17 NOV 2011 | DOI: 10.1111/j.1742-4658.2011.07859.x