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https://www.readbyqxmd.com/read/29688327/structural-and-biochemical-characterization-of-the-protease-domain-of-the-mosaic-botulinum-neurotoxin-type-ha
#1
Kwok-Ho Lam, Stefan Sikorra, Jasmin Weisemann, Hannah Maatsch, Kay Perry, Andreas Rummel, Thomas Binz, Rongsheng Jin
The extreme toxicity of botulinum neurotoxins (BoNTs) relies on their specific cleavage of SNARE proteins, which eventually leads to muscle paralysis. One newly identified mosaic toxin, BoNT/HA (aka H or FA), cleaves VAMP-2 at a unique position between residues L54 and E55, but the molecular basis underlying VAMP-2-recognition of BoNT/HA remains poorly characterized. Here, we report a ∼2.09 Å resolution crystal structure of the light chain protease domain of BoNT/HA (LC/HA). Structural comparison between LC/HA and LC of BoNT/F1 (LC/F1) reveals distinctive hydrophobic and electrostatic features near the active sites, which may explain their different VAMP-2 cleavage sites...
April 23, 2018: Pathogens and Disease
https://www.readbyqxmd.com/read/29687151/anti-cancer-parasporin-toxins-of-new-bacillus-thuringiensis-against-human-colon-hct-116-and-blood-ccrf-cem-cancer-cell-lines
#2
Elham Moazamian, Nima Bahador, Negar Azarpira, Manoochehr Rasouli
Bacillus thuringiensis is one of the most important microorganisms used against cancer cell lines in latest studies all over the world. This study aims to perform the isolation, molecular identification, and to identify novel B. thuringiensis strains that specifically targeting human cancer cell-killing activities in Iran. A total of 88 B. thuringiensis isolates were recovered from Iran. Upon the treatment of the non-hemolytic crystal proteins by proteinase K, five isolates belonging to three biotypes, thuringiensis, kurstaki and sotto of B...
April 23, 2018: Current Microbiology
https://www.readbyqxmd.com/read/29649119/crystal-structure-of-botulinum-neurotoxin-a2-in-complex-with-the-human-protein-receptor-sv2c-reveals-plasticity-in-receptor-binding
#3
Robert Gustafsson, Sicai Zhang, Geoffrey Masuyer, Min Dong, Pål Stenmark
Botulinum neurotoxins (BoNTs) are a family of highly dangerous bacterial toxins, with seven major serotypes (BoNT/A-G). Members of BoNTs, BoNT/A1 and BoNT/B1, have been utilized to treat an increasing number of medical conditions. The clinical trials are ongoing for BoNT/A2, another subtype of BoNT/A, which showed promising therapeutic properties. Both BoNT/A1 and BoNT/A2 utilize three isoforms of synaptic vesicle protein SV2 (SV2A, B, and C) as their protein receptors. We here present a high resolution (2...
April 12, 2018: Toxins
https://www.readbyqxmd.com/read/29624768/gnat-toxins-of-bacterial-toxin-antitoxin-systems-acetylation-of-charged-trnas-to-inhibit-translation
#4
Chew Chieng Yeo
GCN5-related N-acetyltransferase (GNAT) is a huge superfamily of proteins spanning the prokaryotic and eukaryotic domains of life. GNAT proteins usually transfer an acetyl group from acetyl-CoA to a wide variety of substrates ranging from aminoglycoside antibiotics to large macromolecules. Type II toxin-antitoxin (TA) modules are typically bicistronic and widespread in bacterial and archael genomes with diverse cellular functions. Recently, a novel family of type II TA toxins was described which presents a GNAT-fold and functions by acetylating charged tRNA thereby precluding translation...
April 6, 2018: Molecular Microbiology
https://www.readbyqxmd.com/read/29623279/-clostridium-difficile-colitis-leading-to-reactive-arthritis-a-rare-complication-associated-with-a-common-disease
#5
Asghar Marwat, Hassan Mehmood, Ali Hussain, Muzammil Khan, Asad Ullah, Medha Joshi
The relationship between reactive arthritis and enteric infections caused by Yersinia enterocolitica, Campylobacter jejuni , and Salmonella typhimurium is well documented. Clostridium difficile colitis is a less recognized cause of reactive arthritis. We present a case of a 58-year-old woman with Clostridium difficile colitis complicated by reactive arthritis. A 58-year-old woman with no significant past medical history presented to our hospital with complaints of nonbloody watery diarrhea, abdominal pain for the past 1 week, and right knee pain starting 1 day prior...
January 2018: Journal of Investigative Medicine High Impact Case Reports
https://www.readbyqxmd.com/read/29607282/recent-advancement-on-chemical-arsenal-of-bt-toxin-and-its-application-in-pest-management-system-in-agricultural-field
#6
REVIEW
Pritam Chattopadhyay, Goutam Banerjee
Bacillus thuringiensis ( Bt ) is a Gram-positive, spore-forming, soil bacterium, which is very popular bio-control agent in agricultural and forestry. In general, B. thuringiensis secretes an array of insecticidal proteins including toxins produced during vegetative growth phase (such as secreted insecticidal protein, Sip; vegetative insecticidal proteins, Vip), parasporal crystalline δ-endotoxins produced during vegetative stationary phase (such as cytolytic toxin, Cyt; and crystal toxin, Cry), and β-exotoxins...
April 2018: 3 Biotech
https://www.readbyqxmd.com/read/29576992/high-resolution-crystal-structures-of-the-receptor-binding-domain-of-clostridium-botulinum-neurotoxin-serotypes-a-and-fa
#7
Jonathan R Davies, Gavin S Hackett, Sai Man Liu, K Ravi Acharya
The binding specificity of botulinum neurotoxins (BoNTs) is primarily a consequence of their ability to bind to multiple receptors at the same time. BoNTs consist of three distinct domains, a metalloprotease light chain (LC), a translocation domain (HN ) and a receptor-binding domain (HC ). Here we report the crystal structure of HC /FA, complementing an existing structure through the modelling of a previously unresolved loop which is important for receptor-binding. Our HC /FA structure also contains a previously unidentified disulphide bond, which we have also observed in one of two crystal forms of HC /A1...
2018: PeerJ
https://www.readbyqxmd.com/read/29575515/conserved-structural-features-anchor-biofilm-associated-rtx-adhesins-to-the-outer-membrane-of-bacteria
#8
Shuaiqi Guo, David N Langelaan, Sean W Phippen, Steven P Smith, Ilja K Voets, Peter L Davies
Repeats-In-Toxin (RTX) adhesins are present in many Gram-negative bacteria to facilitate biofilm formation. Previously, we reported that the 1.5-MDa RTX adhesin (MpIBP) from the Antarctic bacterium, Marinomonas primoryensis, is tethered to the bacterial cell surface via its N-terminal Region I (RI). Here, we show the detailed structural features of RI. It has an N-terminal periplasmic retention domain (RIN), a central domain (RIM) that can insert into the β-barrel of an outer-membrane pore protein during MpIBP secretion, and three extracellular domains at its C terminus (RIC) that transition the protein into the extender region (RII)...
March 25, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29556063/computational-and-biological-characterization-of-fusion-proteins-of-two-insecticidal-proteins-for-control-of-insect-pests
#9
Shaista Javaid, Sehrish Naz, Imran Amin, Georg Jander, Zaheer Ul-Haq, Shahid Mansoor
Sucking pests pose a serious agricultural challenge, as available transgenic technologies such as Bacillus thuringiensis crystal toxins (Bt) are not effective against them. One approach is to produce fusion protein toxins for the control of these pests. Two protein toxins, Hvt (ω-atracotoxin from Hadronyche versuta) and onion leaf lectin, were translationally fused to evaluate the negative effects of fusion proteins on Phenacoccus solenopsis (mealybug), a phloem-feeding insect pest. Hvt was cloned both N-terminally (HL) and then C-terminally (LH) in the fusion protein constructs, which were expressed transiently in Nicotiana tabacum using a Potato Virus X (PVX) vector...
March 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29555683/structure-function-analyses-reveal-the-molecular-architecture-and-neutralization-mechanism-of-a-bacterial-hepn-mnt-toxin-antitoxin
#10
Xuanyan Jia, Jianyun Yao, Zengqiang Gao, Guangfeng Liu, Yuhui Dong, Xiaoxue Wang, Heng Zhang
Toxin-antitoxin (TA) loci in bacteria are small genetic modules that regulate various cellular activities, including cell growth and death. The two-gene module encoding a HEPN (higher eukaryotes and prokaryotes nucleotide-binding) domain and a cognate MNT (minimal nucleotidyltransferase) domain has been predicted to represent a novel type II TA system prevalent in archaea and bacteria. However, the neutralization mechanism and cellular targets of the TA family remain unclear. The toxin SO_3166 having a HEPN domain and its cognate antitoxin SO_3165 with an MNT domain constitute a typical type II TA system that regulates cell motility and confers plasmid stability in the bacterium Shewanella oneidensis...
March 19, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29544258/toward-multiplexed-quantification-of-biomolecules-on-surfaces-using-time-of-flight-secondary-ion-mass-spectrometry
#11
Louise Wogelred, Fredrik Höök, Björn Agnarsson, Peter Sjövall
Accurate detection and quantification of individual molecules is important for the development of improved diagnostic methods as well as biochemical characterization of disease progression and treatments. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a surface analysis technique capable of imaging the distribution of specific molecules on surfaces with a high spatial resolution (<1 μm) and high sensitivity. ToF-SIMS is particularly suitable for detection of molecules up to ∼2 kDa, including lipids, whereas larger molecules, such as peptides and proteins, are fragmented during analysis, which makes them difficult to identify...
March 15, 2018: Biointerphases
https://www.readbyqxmd.com/read/29543870/dynamics-of-scabin-toxin-a-proposal-for-the-binding-mode-of-the-dna-substrate
#12
Miguel R Lugo, Bronwyn Lyons, Cristina Lento, Derek J Wilson, A Rod Merrill
Scabin is a mono-ADP-ribosyltransferase enzyme and is a putative virulence factor produced by the plant pathogen, Streptomyces scabies. Previously, crystal structures of Scabin were solved in the presence and absence of substrate analogues and inhibitors. Herein, experimental (hydrogen-deuterium exchange), simulated (molecular dynamics), and theoretical (Gaussian Network Modeling) approaches were systematically applied to study the dynamics of apo-Scabin in the context of a Scabin·NAD+·DNA model. MD simulations revealed that the apo-Scabin solution conformation correlates well with the X-ray crystal structure, beyond the conformation of the exposed, mobile regions...
2018: PloS One
https://www.readbyqxmd.com/read/29540745/structural-characterisation-of-the-catalytic-domain-of-botulinum-neurotoxin-x-high-activity-and-unique-substrate-specificity
#13
Geoffrey Masuyer, Sicai Zhang, Sulyman Barkho, Yi Shen, Linda Henriksson, Sara Košenina, Min Dong, Pål Stenmark
Botulinum neurotoxins (BoNTs) are among the most potent toxins known and are also used to treat an increasing number of medical disorders. There are seven well-established serotypes (BoNT/A-G), which all act as zinc-dependent endopeptidases targeting specific members of the SNARE proteins required for synaptic vesicle exocytosis in neurons. A new toxin serotype, BoNT/X, was recently identified. It cleaves not only the canonical targets, vesicle associated membrane proteins (VAMP) 1/2/3 at a unique site, but also has the unique ability to cleave VAMP4/5 and Ykt6...
March 14, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29521542/ocular-permeation-and-sustained-anti-inflammatory-activity-of-dexamethasone-from-kaolin-nanodispersion-hydrogel-system
#14
Arunima Pramanik, Rudra Narayan Sahoo, Ashirbad Nanda, Rajaram Mohapatra, Ranveer Singh, Subrata Mallick
PURPOSE: Kaolin can adhere to the mucosa and protect it by absorbing toxins, bacteria, and viruses. Ocular delivery and anti-inflammatory activity of dexamethasone hydrogel system could be advantageous after kaolin incorporation. METHODS: Hydroxypropyl methylcellulose (HPMC) films of dexamethasone have been prepared without and with kaolin by solvent casting method. Differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and scanning electron microscopy (SEM) were utilized for evaluating thermal property, crystallinity, and morphology of the film preparations respectively...
March 9, 2018: Current Eye Research
https://www.readbyqxmd.com/read/29507107/clec9a-dendritic-cells-are-not-essential-for-antitumor-cd8-t-cell-responses-induced-by-poly-i-c-immunotherapy
#15
Connie B Gilfillan, Sabine Kuhn, Camille Baey, Evelyn J Hyde, Jianping Yang, Christiane Ruedl, Franca Ronchese
In the steady state, tumors harbor several populations of dendritic cells (DCs) and myeloid cells that are key regulators of the intratumoral immune environment. Among these cells, migratory CD103+ cross-presenting DCs are thought to be critical for tumor-specific CTL responses and tumor resistance. However, it is unclear whether this prominent role also extends to immunotherapy. We used a murine orthotopic mammary tumor model, as well as Clec9A-diphtheria toxin receptor mice that can be depleted of the specialized cross-presenting CD8α+ and CD103+ DC1 subsets, to investigate the role of these DCs in immunotherapy...
March 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29502179/nematode-specific-cadherin-cdh-8-acts-as-a-receptor-for-cry5b-toxin-in-caenorhabditis-elegans
#16
Donghai Peng, Danfeng Wan, Chunsheng Cheng, Xiaobo Ye, Ming Sun
Parasitic nematodes of animals and plants cause worldwide devastating impacts on people's lives and agricultural crops. The crystal protein Cry5B produced by Bacillus thuringiensis has efficient and specific activity against a wide range of nematodes. However, the action mode of this toxin has not yet been thoroughly determined. Here, a nematode-specific cadherin CDH-8 was demonstrated to be a receptor for Cry5B toxin by using Caenorhabditis elegans as a model, providing evidence that the cadherin mutant worm cdh-8(RB815) possesses significant resistance to Cry5B, and the CDH-8 fragments bind specifically to Cry5B...
March 3, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29497015/yopt-domain-of-the-pfhb2-toxin-from-pasteurella-multocida-protein-expression-characterization-crystallization-and-crystallographic-analysis
#17
Sanjeev Kumar, Victoria Hedrick, Seema Mattoo
Pasteurella multocida causes respiratory-tract infections in a broad range of animals, as well as opportunistic infections in humans. P. multocida secretes a multidomain toxin called PfhB2, which contains a YopT-like cysteine protease domain at its C-terminus. The YopT domain of PfhB2 contains a well conserved Cys-His-Asp catalytic triad that defines YopT family members, and shares high sequence similarity with the prototype YopT from Yersinia sp. To date, only one crystal structure of a YopT family member has been reported; however, additional structural information is needed to help characterize the varied substrate specificity and enzymatic action of this large protease family...
March 1, 2018: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/29494518/structural-basis-for-the-specific-neutralization-of-stx2a-with-a-camelid-single-domain-antibody-fragment
#18
Robert Alvin Bernedo-Navarro, Ema Romão, Tomomasa Yano, Joar Pinto, Henri De Greve, Yann G-J Sterckx, Serge Muyldermans
BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) are a subset of pathogens leading to illnesses such as diarrhea, hemolytic uremic syndrome and even death. The Shiga toxins are the main virulence factors and divided in two groups: Stx1 and Stx2, of which the latter is more frequently associated with severe pathologies in humans. RESULTS: An immune library of nanobodies (Nbs) was constructed after immunizing an alpaca with recombinant Shiga toxin-2a B subunit (rStx2aB), to retrieve multiple rStx2aB-specific Nbs...
March 1, 2018: Toxins
https://www.readbyqxmd.com/read/29461656/identification-and-characterization-of-acetyltransferase-type-toxin-antitoxin-loci-in-klebsiella-pneumoniae
#19
Hongliang Qian, Qingqing Yao, Cui Tai, Zixin Deng, Jianhua Gan, Hong-Yu Ou
A type II toxin-antitoxin (TA) system, in which the toxin contains a Gcn5-related N-acetyltransferase (GNAT) domain, has been characterized recently. GNAT toxin acetylates aminoacyl-tRNA and blocks protein translation. It is abolished by the cognate antitoxin that contains the ribbon-helix-helix (RHH) domain. Here, we present an experimental demonstration of the interaction of the GNAT-RHH complex with TA promoter DNA. First, the GNAT-RHH TA locus kacAT was found in Klebsiella pneumoniae HS11286, a strain resistant to multiple antibiotics...
February 20, 2018: Molecular Microbiology
https://www.readbyqxmd.com/read/29432487/structural-basis-of-mammalian-glycan-targeting-by-vibrio-cholerae-cytolysin-and-biofilm-proteins
#20
Swastik De, Katherine Kaus, Shada Sinclair, Brandon C Case, Rich Olson
Vibrio cholerae is an aquatic gram-negative microbe responsible for cholera, a pandemic disease causing life-threatening diarrheal outbreaks in populations with limited access to health care. Like most pathogenic bacteria, V. cholerae secretes virulence factors to assist colonization of human hosts, several of which bind carbohydrate receptors found on cell-surfaces. Understanding how pathogenic virulence proteins specifically target host cells is important for the development of treatment strategies to fight bacterial infections...
February 12, 2018: PLoS Pathogens
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