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https://www.readbyqxmd.com/read/27903650/structural-analysis-of-single-domain-antibodies-bound-to-a-second-neutralizing-hot-spot-on-ricin-toxin-s-enzymatic-subunit
#1
Michael J Rudolph, David J Vance, Michael S Cassidy, Yinghui Rong, Nicholas J Mantis
Ricin toxin is a heterodimer consisting of RTA, a ribosome-inactivating protein, and RTB, a lectin that facilitates receptor-mediated uptake into mammalian cells. In previous studies, we demonstrated that toxin-neutralizing antibodies target four spatially distinct hotspots on RTA, which we refer to as epitope Clusters I-IV. In this report we identified and characterized three single domain camelid antibodies (VHH) against Cluster II. One of these VHHs, V5E1, ranks as one of the most potent ricin-neutralizing antibodies described to date...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27847174/protective-efficacy-of-a-novel-alpha-hemolysin-subunit-vaccine-at62-against-staphylococcus-aureus-skin-and-soft-tissue-infections
#2
Rajan P Adhikari, Christopher D Thompson, M Javad Aman, Jean C Lee
Alpha hemolysin (Hla) is a pore-forming toxin produced by most Staphylococcus aureus isolates. Hla is reported to play a key role in the pathogenesis of staphylococcal infections, such as skin and soft tissue infection, pneumonia, and lethal peritonitis. This study makes use of a novel recombinant subunit vaccine candidate (AT62) that was rationally designed based on the Hla heptameric crystal structure. AT62 comprises a critical structural domain at the N terminus of Hla, and it has no inherent toxic properties...
December 7, 2016: Vaccine
https://www.readbyqxmd.com/read/27819327/structure-and-function-of-fs50-a-salivary-protein-from-the-flea-xenopsylla-cheopis-that-blocks-the-sodium-channel-nav1-5
#3
Xueqing Xu, Bei Zhang, Shilong Yang, Su An, José M C Ribeiro, John F Andersen
Naturally occurring toxins have been invaluable tools for the study of structural and functional relationships of voltage-gated sodium channels (VGSC). Few studies have been made of potential channel-modulating substances from blood-feeding arthropods. He we describe the characterization FS50, a salivary protein from the flea, Xenopsylla cheopis, that exhibits an inhibitory activity against the NaV1.5 channel with an IC50 of 1.58 μM. The pore-blocking mechanism of this toxin is evident from the kinetics of activation and inactivation suggesting that FS50 does not interfere with the voltage sensor of NaV1...
November 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27807200/molecular-determinants-of-bk-channel-functional-diversity-and-functioning
#4
REVIEW
Ramon Latorre, Karen Castillo, Willy Carrasquel-Ursulaez, Romina V Sepulveda, Fernando Gonzalez-Nilo, Carlos Gonzalez, Osvaldo Alvarez
Large-conductance Ca(2+)- and voltage-activated K(+) (BK) channels play many physiological roles ranging from the maintenance of smooth muscle tone to hearing and neurosecretion. BK channels are tetramers in which the pore-forming α subunit is coded by a single gene (Slowpoke, KCNMA1). In this review, we first highlight the physiological importance of this ubiquitous channel, emphasizing the role that BK channels play in different channelopathies. We next discuss the modular nature of BK channel-forming protein, in which the different modules (the voltage sensor and the Ca(2+) binding sites) communicate with the pore gates allosterically...
January 2017: Physiological Reviews
https://www.readbyqxmd.com/read/27783504/the-remarkable-character-of-porphobilinogen-synthase
#5
Eileen K Jaffe
Porphobilinogen synthase (PBGS), also known as 5-aminolevulinate dehydratase, is an essential enzyme in the biosynthesis of all tetrapyrroles, which function in respiration, photosynthesis, and methanogenesis. Throughout evolution, PBGS adapted to a diversity of cellular niches and evolved to use an unusual variety of metal ions both for catalytic function and to control protein multimerization. With regard to the active site, some PBGSs require Zn(2+); a subset of those, including human PBGS, contain a constellation of cysteine residues that acts as a sink for the environmental toxin Pb(2+)...
October 26, 2016: Accounts of Chemical Research
https://www.readbyqxmd.com/read/27774510/robotic-qm-mm-driven-maturation-of-antibody-combining-sites
#6
Ivan V Smirnov, Andrey V Golovin, Spyros D Chatziefthimiou, Anastasiya V Stepanova, Yingjie Peng, Olga I Zolotareva, Alexey A Belogurov, Inna N Kurkova, Natalie A Ponomarenko, Matthias Wilmanns, G Michael Blackburn, Alexander G Gabibov, Richard A Lerner
In vitro selection of antibodies from large repertoires of immunoglobulin (Ig) combining sites using combinatorial libraries is a powerful tool, with great potential for generating in vivo scavengers for toxins. However, addition of a maturation function is necessary to enable these selected antibodies to more closely mimic the full mammalian immune response. We approached this goal using quantum mechanics/molecular mechanics (QM/MM) calculations to achieve maturation in silico. We preselected A17, an Ig template, from a naïve library for its ability to disarm a toxic pesticide related to organophosphorus nerve agents...
October 2016: Science Advances
https://www.readbyqxmd.com/read/27769815/parasporins-1-and-2-their-structure-and-activity
#7
Toshihiko Akiba, Shiro Okumura
Parasporins are novel protein toxins preferentially cytotoxic against human cancer cells. They are obtained from parasporal inclusions of Bacillus thuringiensis and, accordingly, are considered congeners of the insecticidal Cry toxins. Two types of parasporins have been identified: the three-domain Cry toxin type and the β-pore-forming-toxin (β-PFT) type. Crystal structures of representative members of the two types, PS1Aa1 and PS2Aa1, have been determined and compared with those of well-studied toxins. PS1Aa1 has a typical architecture characteristic of the three-domain insecticidal Cry toxins, though it is cleaved into two polypeptides...
October 18, 2016: Journal of Invertebrate Pathology
https://www.readbyqxmd.com/read/27754366/crystal-structure-of-ribosome-inactivating-protein-ricin-a-chain-in-complex-with-the-c-terminal-peptide-of-the-ribosomal-stalk-protein-p2
#8
Wei-Wei Shi, Yun-Sang Tang, See-Yuen Sze, Zhen-Ning Zhu, Kam-Bo Wong, Pang-Chui Shaw
Ricin is a type 2 ribosome-inactivating protein (RIP), containing a catalytic A chain and a lectin-like B chain. It inhibits protein synthesis by depurinating the N-glycosidic bond at α-sarcin/ricin loop (SRL) of the 28S rRNA, which thereby prevents the binding of elongation factors to the GTPase activation center of the ribosome. Here, we present the 1.6 Å crystal structure of Ricin A chain (RTA) complexed to the C-terminal peptide of the ribosomal stalk protein P2, which plays a crucial role in specific recognition of elongation factors and recruitment of eukaryote-specific RIPs to the ribosomes...
October 13, 2016: Toxins
https://www.readbyqxmd.com/read/27751850/crystal-structure-of-the-adp-ribosylating-component-of-bec-the-binary-enterotoxin-of-clostridium-perfringens
#9
Kazuki Kawahara, Shinya Yonogi, Ryota Munetomo, Hiroya Oki, Takuya Yoshida, Yuko Kumeda, Shigeaki Matsuda, Toshio Kodama, Tadayasu Ohkubo, Tetsuya Iida, Shota Nakamura
Binary enterotoxin of Clostridium perfringens (BEC), consisting of the components BECa and BECb, was recently identified as a novel enterotoxin produced by C. perfringens that causes acute gastroenteritis in humans. Although the detailed mechanism of cell intoxication by BEC remains to be defined, BECa shows both NAD(+)-glycohydrolase and actin ADP-ribosyltransferase activities in the presence of NAD(+). In this study, we determined the first crystal structure of BECa in its apo-state and in complex with NADH...
October 14, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27715009/crystal-structure-of-os79-os04g0206600-from-oryza-sativa-a-udp-glucosyltransferase-involved-in-the-detoxification-of-deoxynivalenol
#10
Karl M Wetterhorn, Sean A Newmister, Rachell K Caniza, Mark Busman, Susan Patricia McCormick, Franz Berthiller, Gerhard Adam, Ivan Rayment
Fusarium head blight is a plant disease with significant agricultural and health impacts which affects cereal crops such as wheat, barley, and maize, and is characterized by reduced grain yield and the accumulation of trichothecene mycotoxins such as deoxynivalenol (DON). Studies have identified trichothecene production as a virulence factor in Fusarium graminearum, and have linked DON resistance to the ability to form DON-3-O-glucoside in wheat. Here, the structures of a deoxynivalenol:UDP-glucosyltransferase (Os79) from Oryza sativa are reported in complex with UDP in an open conformation, in complex with UDP in a closed conformation, and in complex with UDP-2-fluoro-2-deoxy-D-glucose and trichothecene at 1...
October 7, 2016: Biochemistry
https://www.readbyqxmd.com/read/27713959/a-chitosan-coated-liposome-encapsulating-antibacterial-peptide-apep10-characterisation-triggered-release-effects-and-antilisterial-activity-in-thaw-water-of-frozen-chicken
#11
Chuanfen Pu, Wenting Tang
Contamination of Listeria monocytogenes in food and their processing environment is a focus of attention in the food industry. To achieve the controlled release of antibacterial agents to a food processing environment contaminated by L. monocytogenes, chitosan-stabilised liposomes encapsulating Apep10 (GLARCLAGTL), an antibacterial peptide derived from boiled-dried anchovies, were prepared by utilising listeria toxins to activate the peptide release. Characteristics including the particle size, polydispersity index (PDI), encapsulation efficiency (EE), and morphology of the chitosan-coated Apep10 liposomes were investigated...
October 12, 2016: Food & Function
https://www.readbyqxmd.com/read/27698444/structure-and-specificity-of-the-type-vi-secretion-system-clpv-tssc-interaction-in-enteroaggregative-escherichia-coli
#12
Badreddine Douzi, Yannick R Brunet, Silvia Spinelli, Valentine Lensi, Pierre Legrand, Stéphanie Blangy, Anant Kumar, Laure Journet, Eric Cascales, Christian Cambillau
The Type VI secretion system (T6SS) is a versatile machine that delivers toxins into either eukaryotic or bacterial cells. It thus represents a key player in bacterial pathogenesis and inter-bacterial competition. Schematically, the T6SS can be viewed as a contractile tail structure anchored to the cell envelope. The contraction of the tail sheath propels the inner tube loaded with effectors towards the target cell. The components of the contracted tail sheath are then recycled by the ClpV AAA(+) ATPase for a new cycle of tail elongation...
October 4, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27693093/complete-genome-sequence-of-bacillus-thuringiensis-serovar-alesti-bgsc-4c1-a-typical-strain-with-toxicity-to-lepidoptera-insects
#13
Yueying Wang, Jingjing Fu, Qian Zhu, Lei Zhu, Jinshui Zheng, Hualin Liu, Donghai Peng, Lifang Ruan, Ming Sun
Bacillus thuringiensis serovar alesti was used to control caterpillars from 1970s. Here we reported the complete genome of BGSC 4C1, the type strain of this serovar. It has a circular chromosome and six plasmids. The largest plasmid pBMB267 contains five insecticidal crystal protein genes (two copies of cry1Ae, cry1Gb, cry2Ab, and a novel cry1M-type gene) and three vegetative insecticidal protein genes (a novel binary toxin gene operon vip1-vip2 and vip3Aa). Besides, the strain also has many genes encodeing virulence factors, and some secondary metabolite biosynthetic gene clusters involved in synthesis of antimicrobial peptides and bacteriocins...
September 28, 2016: Journal of Biotechnology
https://www.readbyqxmd.com/read/27682503/the-solvent-exposed-c-terminus-of-the-cytolysin-a-pore-forming-toxin-directs-pore-formation-and-channel-function-in-membranes
#14
Pradeep Sathyanarayana, Rajat Desikan, K Ganapathy Ayappa, Sandhya S Visweswariah
Pore-forming toxins (PFTs) bind to cell membranes and form nanoscale pores that allow leakage of cellular components, resulting in cell death. The water-soluble, monomeric form of these toxins shows a dramatic conformational change during pore formation, as exemplified by crystal structures of the monomer and functional pore of cytolysin A (ClyA). The solvent-exposed, C-terminal residues of the protein are essential for activity, but the mechanism by which this region regulates pore formation remains unknown...
October 13, 2016: Biochemistry
https://www.readbyqxmd.com/read/27680699/de-novo-phasing-with-x-ray-laser-reveals-mosquito-larvicide-binab-structure
#15
Jacques-Philippe Colletier, Michael R Sawaya, Mari Gingery, Jose A Rodriguez, Duilio Cascio, Aaron S Brewster, Tara Michels-Clark, Robert H Hice, Nicolas Coquelle, Sébastien Boutet, Garth J Williams, Marc Messerschmidt, Daniel P DePonte, Raymond G Sierra, Hartawan Laksmono, Jason E Koglin, Mark S Hunter, Hyun-Woo Park, Monarin Uervirojnangkoorn, Dennis K Bideshi, Axel T Brunger, Brian A Federici, Nicholas K Sauter, David S Eisenberg
BinAB is a naturally occurring paracrystalline larvicide distributed worldwide to combat the devastating diseases borne by mosquitoes. These crystals are composed of homologous molecules, BinA and BinB, which play distinct roles in the multi-step intoxication process, transforming from harmless, robust crystals, to soluble protoxin heterodimers, to internalized mature toxin, and finally to toxic oligomeric pores. The small size of the crystals-50 unit cells per edge, on average-has impeded structural characterization by conventional means...
September 28, 2016: Nature
https://www.readbyqxmd.com/read/27647868/progress-towards-the-development-of-a-neat-protein-vaccine-for-anthrax-disease
#16
Miriam A Balderas, Chinh Nguyen, Austen Terwilliger, Wendy A Keitel, Angelina Iniguez, Rodrigo Torres, Frederico Palacios, Celia W Goulding, Anthony W Maresso
Bacillus anthracis is a sporulating Gram-positive bacterium that is the causative agent of anthrax and a potential weapon of bioterrorism. The U.S. licensed anthrax vaccine is made from an incompletely characterized culture supernatant of a nonencapsulated, toxigenic strain (anthrax vaccine absorbed - AVA) whose primary protective component is thought to be protective antigen (PA). AVA is effective in protecting animals and elicits toxin-neutralizing antibodies in humans, but enthusiasm is dampened by its undefined composition, multi-shot regimen, recommended boosters, and potential for adverse reactions...
September 19, 2016: Infection and Immunity
https://www.readbyqxmd.com/read/27628909/effects-and-mechanisms-of-bacillus-thuringiensis-crystal-toxins-for-mosquito-larvae
#17
Qi Zhang, Gang Hua, Michael J Adang
Bacillus thuringiensis is a gram-positive aerobic bacterium that produces insecticidal crystalline inclusions during sporulation phases of the mother cell. The virulence factor, known as parasporal crystals, is composed of Cry and Cyt toxins. Cry toxins display a common three-domain topology. Cry toxins exert intoxication through toxin activation, receptor binding and pore formation in suitable larval gut environment. The mosquitocidal toxins, Bt subsp. israelensis (Bti) and was found highly active against mosquito larvae and are widely used in pesticide market for vector control...
September 15, 2016: Insect Science
https://www.readbyqxmd.com/read/27618477/rare-cause-of-facial-palsy-case-report-of-tick-paralysis-by-ixodes-holocyclus-imported-by-a-patient-travelling-into-singapore-from-australia
#18
Chong Han Pek, Crystal Shuk Jin Cheong, Yan Lin Yap, Stephen Doggett, Thiam Chye Lim, Wei Chen Ong, Jane Lim
BACKGROUND: Ticks are blood-sucking arachnids that feed on all classes of vertebrates, including humans. Ixodes holocyclus, also known as the Australian Paralysis Tick, is capable of causing a myriad of clinical issues in humans and companion animals, including the transmission of infectious agents, toxin-mediated paralysis, allergic and inflammatory reactions, and mammalian meat allergies in humans. The Australian Paralysis Tick is endemic to Australia, and only two other exported cases have been reported in the literature...
September 8, 2016: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/27601326/structural-insight-into-the-e-%C3%A2-coli-higba-complex
#19
Jingsi Yang, Ke Zhou, Peng Liu, Yuhui Dong, Zengqiang Gao, Jianjun Zhang, Quansheng Liu
The toxin-antitoxin system is ubiquitously existed in bacteria and archaea, performing a wide variety of functions modulating cell fitness in response to environmental cues. In this report, we solved the crystal structure of the toxin-antitoxin HigBA complex from E. coli K-12 to 2.7 Å resolution. The crystal structure of the HigBA complex displays a hetero-tetramer (HigBA)2 form comprised by two HigB and two HigA subunits. Each toxin HigB resumes a microbial RNase T1 fold, characteristic of a three antiparallel β-sheet core shielded by a few α-helices at either side...
September 30, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27599865/1-65%C3%A2-%C3%A3-resolution-structure-of-the-arac-family-transcriptional-activator-toxt-from-vibrio-cholerae
#20
Jiaqin Li, Graham Wehmeyer, Scott Lovell, Kevin P Battaile, Susan M Egan
ToxT is an AraC-family transcriptional activator protein that controls the expression of key virulence factors in Vibrio cholerae, the causative agent of cholera. ToxT directly activates the expression of the genes that encode the toxin-coregulated pilus and cholera toxin, and also positively auto-regulates its own expression from the tcp promoter. The crystal structure of ToxT has previously been solved at 1.9 Å resolution (PDB entry 3gbg). In this study, a crystal structure of ToxT at 1.65 Å resolution with a similar overall structure to the previously determined structure is reported...
September 2016: Acta Crystallographica. Section F, Structural Biology Communications
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