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https://www.readbyqxmd.com/read/28433497/clostridium-difficile-toxin-glucosyltransferase-domains-in-complex-with-a-non-hydrolyzable-udp-glucose-analogue
#1
Joseph W Alvin, D Borden Lacy
Clostridium difficile is the leading cause of hospital-acquired diarrhea and pseudomembranous colitis worldwide. The organism produces two homologous toxins, TcdA and TcdB, which enter and disrupt host cell function by glucosylating and thereby inactivating key signalling molecules within the host. As a toxin-mediated disease, there has been a significant interest in identifying small molecule inhibitors of the toxins' glucosyltransferase activities. This study was initiated as part of an effort to identify the mode of inhibition for a small molecule inhibitor of glucosyltransferase activity called apigenin...
April 19, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28414448/substrate-profiling-and-high-resolution-co-complex-crystal-structure-of-a-secreted-c11-protease-conserved-across-commensal-bacteria
#2
Emily J Roncase, Clara Moon, Sandip Chatterjee, Gonzalo E González-Páez, Charles S Craik, Anthony J O'Donoghue, Dennis W Wolan
Cysteine proteases are among the most abundant hydrolytic enzymes produced by bacteria, and this diverse family of proteins have significant biological roles in bacterial viability and environmental interactions. Members of the clostripain-like (C11) family of cysteine proteases from distal gut commensal strains have recently been shown to mediate immune responses by inducing neutrophil phagocytosis and activating bacterial pathogenic toxins. Development of substrates, inhibitors, and probes that target C11 proteases from enteric bacteria will help to establish the role of these proteins at the interface of the host and microbiome in health and disease...
April 17, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28400471/a-novel-tarantula-toxin-stabilizes-the-deactivated-voltage-sensor-of-bacterial-sodium-channel
#3
Cheng Tang, Xi Zhou, Phuong Tran Nguyen, Yunxiao Zhang, Zhaotun Hu, Changxin Zhang, Vladimir Yarov-Yarovoy, Paul G DeCaen, Songping Liang, Zhonghua Liu
Voltage-gated sodium channels (NaVs) are activated by transiting the voltage sensor from the deactivated to the activated state. The crystal structures of several bacterial NaVs have captured the voltage sensor module (VSM) in an activated state, but structure of the deactivated voltage sensor remains elusive. In this study, we sought to identify peptide toxins stabilizing the deactivated VSM of bacterial NaVs. We screened fractions from several venoms and characterized a cystine knot toxin called JZTx-27 from the venom of tarantula Chilobrachys jingzhao as a high-affinity antagonist of the prokaryotic NaVs nonselective voltage-gated, Bacillus alcalophilus (NsVBa) and bacterial sodium channel from Bacillus halodurans(NaChBac) (IC50 = 112 nM and 30 nM, respectively)...
April 11, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28398546/the-cdi-toxin-ofyersinia-kristensenii-is-a-novel-bacterial-member-of-the-rnase-a-superfamily
#4
Gaëlle Batot, Karolina Michalska, Greg Ekberg, Ervin M Irimpan, Grazyna Joachimiak, Robert Jedrzejczak, Gyorgy Babnigg, Christopher S Hayes, Andrzej Joachimiak, Celia W Goulding
Contact-dependent growth inhibition (CDI) is an important mechanism of inter-bacterial competition found in many Gram-negative pathogens. CDI+ cells express cell-surface CdiA proteins that bind neighboring bacteria and deliver C-terminal toxin domains (CdiA-CT) to inhibit target-cell growth. CDI+ bacteria also produce CdiI immunity proteins, which specifically neutralize cognate CdiA-CT toxins to prevent self-inhibition. Here, we present the crystal structure of the CdiA-CT/CdiIYkris complex from Yersinia kristensenii ATCC 33638...
April 10, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28351618/structure-of-the-mazf-mt9-toxin-a-trna-specific-endonuclease-from-mycobacterium-tuberculosis
#5
Ran Chen, Jie Tu, Zhihui Liu, Fanrong Meng, Pinyun Ma, Zhishan Ding, Chengwen Yang, Lei Chen, Xiangyu Deng, Wei Xie
Tuberculosis (TB) is a severe disease caused by Mycobacterium tuberculosis (M. tb) and the well-characterized M. tb MazE/F proteins play important roles in stress adaptation. Recently, the MazF-mt9 toxin has been found to display endonuclease activities towards tRNAs but the mechanism is unknown. We hereby present the crystal structure of apo-MazF-mt9. The enzyme recognizes tRNA(Lys) with a central UUU motif within the anticodon loop, but is insensitive to the sequence context outside of the loop. Based on our crystallographic and biochemical studies, we identified key residues for catalysis and proposed the potential tRNA-binding site...
March 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28350474/detachment-of-membrane-bound-virions-by-competitive-ligand-binding-induced-receptor-depletion
#6
Nagma Parveen, Stephan Block, Vladimir P Zhdanov, Gustaf E Rydell, Fredrik Höök
Multivalent receptor-mediated interactions between virions and a lipid membrane can be weakened using competitive nonpathogenic ligand binding. In particular, the subsequent binding of such ligands can induce detachment of bound virions, a phenomenon of crucial relevance for the development of new antiviral drugs. Focusing on the simian virus 40 (SV40) and recombinant cholera toxin B subunit (rCTB), and using (monosialotetrahexosyl)ganglioside (GM1) as their common receptor in a supported lipid bilayer (SLB), we present the first detailed investigation of this phenomenon by employing the quartz crystal microbalance with dissipation (QCM-D) and total internal reflection fluorescence (TIRF) microscopy assisted 2D single particle tracking (SPT) techniques...
April 12, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28334932/ribosome-dependent-vibrio-cholerae-mrnase-higb2-is-regulated-by-a-%C3%AE-strand-sliding-mechanism
#7
San Hadži, Abel Garcia-Pino, Sarah Haesaerts, Dukas Jurenas, Kenn Gerdes, Jurij Lah, Remy Loris
Toxin-antitoxin (TA) modules are small operons involved in bacterial stress response and persistence. higBA operons form a family of TA modules with an inverted gene organization and a toxin belonging to the RelE/ParE superfamily. Here, we present the crystal structures of chromosomally encoded Vibrio cholerae antitoxin (VcHigA2), toxin (VcHigB2) and their complex, which show significant differences in structure and mechanisms of function compared to the higBA module from plasmid Rts1, the defining member of the family...
February 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28330277/classical-and-bayesian-predictions-applied-to-bacillus-toxin-production
#8
Karim Ennouri, Rayda Ben Ayed, Maura Mazzarello, Ennio Ottaviani, Fathi Hertelli, Hichem Azzouz
Bacillus thuringiensis is a bacterium with unusual properties that make it useful for pest control in ecoagriculture. It can form a parasporal crystal containing polypeptides (also called delta-endotoxins). These entomopathogenic toxins are made during the stationary phase of the bacterial growth cycle and were initially characterized as an insect pathogen. Nowadays, the use of saturated two-level designs is very popular. This method is especially used in industrial applications where the cost of experiments is expensive...
December 2016: 3 Biotech
https://www.readbyqxmd.com/read/28298445/the-structure-and-function-of-mycobacterium-tuberculosis-mazf-mt6-provides-insights-into-conserved-features-of-mazf-endonucleases
#9
Eric D Hoffer, Stacey J Miles, Christine M Dunham
Toxin-antitoxin systems are ubiquitous in prokaryotic and archaea genomes and regulate growth in response to stress. E. coli contains at least 36 putative toxin-antitoxin gene pairs, and some pathogens such as Mycobacterium tuberculosis (Mtb) have over 90 toxin-antitoxin operons. E. coli MazF cleaves free mRNA after encountering stress and nine Mtb MazF family members cleave mRNA, tRNA, or rRNA. Moreover, Mtb MazF-mt6 cleaves 23S rRNA Helix 70 to inhibit protein synthesis. The overall tertiary folds of these MazFs are predicted to be similar, therefore it is unclear how they recognize structurally distinct RNAs...
March 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28292241/microbial-pest-control-agents-are-they-a-specific-and-safe-tool-for-insect-pest-management
#10
Caroline Deshayes, Myriam Siegwart, David Pauron, Josy-Anne Froger, Bruno Lapied, Véronique Apaire-Marchais
Microorganisms (viruses, bacteria and fungi) or their bioactive agents can be used as active substances and therefore are referred as Microbial Pest Control Agents (MPCA). They are used as alternative strategies to chemical insecticides to counteract the development of resistances and to reduce adverse effects on both environment and human health. These natural entomopathogenic agents, which have specific modes of action, are generally considered safer as compared to conventional chemical insecticides. Baculoviruses are the only viruses being used as the safest biological control agents...
March 14, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28282927/in-vivo-crystallization-of-three-domain-cry-toxins
#11
REVIEW
Rooma Adalat, Faiza Saleem, Neil Crickmore, Shagufta Naz, Abdul Rauf Shakoori
Bacillus thuringiensis (Bt) is the most successful, environmentally-friendly, and intensively studied microbial insecticide. The major characteristic of Bt is the production of proteinaceous crystals containing toxins with specific activity against many pests including dipteran, lepidopteran, and coleopteran insects, as well as nematodes, protozoa, flukes, and mites. These crystals allow large quantities of the protein toxins to remain stable in the environment until ingested by a susceptible host. It has been previously established that 135 kDa Cry proteins have a crystallization domain at their C-terminal end...
March 9, 2017: Toxins
https://www.readbyqxmd.com/read/28282873/crystal-structure-of-the-receptor-binding-domain-of-botulinum-neurotoxin-type-ha-also-known-as-type-fa-or-h
#12
Guorui Yao, Kwok-Ho Lam, Kay Perry, Jasmin Weisemann, Andreas Rummel, Rongsheng Jin
Botulinum neurotoxins (BoNTs), which have been exploited as cosmetics and muscle-disorder treatment medicines for decades, are well known for their extreme neurotoxicity to humans. They pose a potential bioterrorism threat because they cause botulism, a flaccid muscular paralysis-associated disease that requires immediate antitoxin treatment and intensive care over a long period of time. In addition to the existing seven established BoNT serotypes (BoNT/A-G), a new mosaic toxin type termed BoNT/HA (aka type FA or H) was reported recently...
March 8, 2017: Toxins
https://www.readbyqxmd.com/read/28243889/-1-h-13-c-15-n-backbone-assignment-of-the-human-heat-labile-enterotoxin-b-pentamer-and-chemical-shift-mapping-of-neolactotetraose-binding
#13
Daniel Hatlem, Julie E Heggelund, Daniel Burschowsky, Ute Krengel, Per E Kristiansen
The major virulence factor of enterotoxigenic Escherichia coli is the heat-labile enterotoxin (LT), an AB5 toxin closely related to the cholera toxin. LT consists of six subunits, the catalytically active A-subunit and five B-subunits arranged as a pentameric ring (LTB), which enable the toxin to bind to the epithelial cells in the intestinal lumen. LTB has two recognized binding sites; the primary binding site is responsible for anchoring the toxin to its main receptor, the GM1-ganglioside, while the secondary binding site recognizes blood group antigens...
February 27, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28213222/development-of-a-qcm-d-biosensor-for-ochratoxin-a-detection-in-red-wine
#14
Aleksandra Karczmarczyk, Karsten Haupt, Karl-Heinz Feller
Ochratoxin A (OTA), a highly toxic compound, is one of the most widely spread mycotoxins that contaminates a large variety of agricultural commodities. Due to its presence in the food chain, it imposes a hazard on both human and animal health. Therefore, there is a need for precise, fast and simple methods for toxin quantification. Herein, a novel sensor based on a quartz crystal microbalance with dissipation monitoring (QCM-D) and antibodies for specific analyte recognition was developed for rapid and sensitive detection of OTA in red wine...
May 1, 2017: Talanta
https://www.readbyqxmd.com/read/28199340/crystal-structure-and-structure-based-mutagenesis-of-actin-specific-adp-ribosylating-toxin-cpile-a-as-novel-enterotoxin
#15
Waraphan Toniti, Toru Yoshida, Toshiharu Tsurumura, Daisuke Irikura, Chie Monma, Yoichi Kamata, Hideaki Tsuge
Unusual outbreaks of food poisoning in Japan were reported in which Clostridium perfringens was strongly suspected to be the cause based on epidemiological information and fingerprinting of isolates. The isolated strains lack the typical C. perfringens enterotoxin (CPE) but secrete a new enterotoxin consisting of two components: C. perfringens iota-like enterotoxin-a (CPILE-a), which acts as an enzymatic ADP-ribosyltransferase, and CPILE-b, a membrane binding component. Here we present the crystal structures of apo-CPILE-a, NAD+-CPILE-a and NADH-CPILE-a...
2017: PloS One
https://www.readbyqxmd.com/read/28179499/structural-mechanistic-and-functional-insight-into-gliotoxin-bis-thiomethylation-in-aspergillus-fumigatus
#16
Stephen K Dolan, Tobias Bock, Vanessa Hering, Rebecca A Owens, Gary W Jones, Wulf Blankenfeldt, Sean Doyle
Gliotoxin is an epipolythiodioxopiperazine (ETP) class toxin, contains a disulfide bridge that mediates its toxic effects via redox cycling and is produced by the opportunistic fungal pathogen Aspergillus fumigatus Self-resistance against gliotoxin is effected by the gliotoxin oxidase GliT, and attenuation of gliotoxin biosynthesis is catalysed by gliotoxin S-methyltransferase GtmA. Here we describe the X-ray crystal structures of GtmA-apo (1.66 Å), GtmA complexed to S-adenosylhomocysteine (1.33 Å) and GtmA complexed to S-adenosylmethionine (2...
February 2017: Open Biology
https://www.readbyqxmd.com/read/28168605/synergistic-activity-between-s-layer-protein-and-spore-crystal-preparations-from-lysinibacillus-sphaericus-against-culex-quinquefasciatus-larvae
#17
Lucía C Lozano, Jenny Dussán
Lysinibacillus sphaericus is used for the biological control of mosquitoes. The main toxicity mechanism of pathogenic strains is a binary toxin produced during sporulation. S-layer is a proteinaceous structure on the surface of bacteria; its functions have been involved in the interaction between bacterial cells and the environment, for example, as protective coats, surface recognition, and biological control. In L. sphaericus, S-layer protein (SlpC) is expressed in vegetative cells, and is also found in spore-crystal preparations; it has larvicidal activity in Culex spp...
March 2017: Current Microbiology
https://www.readbyqxmd.com/read/28144706/pest-management-through-bacillus-thuringiensis-bt-in-a-tea-silkworm-ecosystem-status-and-potential-prospects
#18
REVIEW
Kavya Dashora, Somnath Roy, Akanksha Nagpal, Sudipta Mukhopadhyay Roy, Julie Flood, Anjali Km Prasad, Ravinder Khetarpal, Suzanne Neave, N Muraleedharan
Bacillus thuringiensis (Bt) is a soil bacterium that forms spores containing crystals comprising one or more Cry or Cyt proteins having potential and specific insecticidal activity. Different strains of Bt produce different types of toxins, affecting a narrow taxonomic group of insects. Therefore, it is used in non-chemical pest management, including inherent pest resistance through GM crops. The specificity of action of Bt toxins reduces the concern of adverse effects on non-target species, a concern which remains with chemical insecticides as well...
March 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28137883/tir-only-protein-rba1-recognizes-a-pathogen-effector-to-regulate-cell-death-in-arabidopsis
#19
Marc T Nishimura, Ryan G Anderson, Karen A Cherkis, Terry F Law, Qingli L Liu, Mischa Machius, Zachary L Nimchuk, Li Yang, Eui-Hwan Chung, Farid El Kasmi, Michael Hyunh, Erin Osborne Nishimura, John E Sondek, Jeffery L Dangl
Detection of pathogens by plants is mediated by intracellular nucleotide-binding site leucine-rich repeat (NLR) receptor proteins. NLR proteins are defined by their stereotypical multidomain structure: an N-terminal Toll-interleukin receptor (TIR) or coiled-coil (CC) domain, a central nucleotide-binding (NB) domain, and a C-terminal leucine-rich repeat (LRR). The plant innate immune system contains a limited NLR repertoire that functions to recognize all potential pathogens. We isolated Response to the bacterial type III effector protein HopBA1 (RBA1), a gene that encodes a TIR-only protein lacking all other canonical NLR domains...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28118708/pegylation-enhances-mosquito-larvicidal-activity-of-lysinibacillus-sphaericus-binary-toxin
#20
Mahima Sharma, Ramesh S Hire, Ashok B Hadapad, Gagan D Gupta, Vinay Kumar
Toxic strains of Lysinibacillus sphaericus have been used in the field for larval control of mosquito vector diseases. The high toxicity of L. sphaericus is attributed to the binary (BinAB) toxin produced as parasporal crystalline inclusions during the early stages of sporulation. BinA and BinB, the primary components of these spore-crystals, exert high toxicity when administered together. However, instability, short half-lives, and rapid proteolytic digestion can limit their use as an effective insecticide...
February 2, 2017: Bioconjugate Chemistry
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