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https://www.readbyqxmd.com/read/28718923/using-homology-modeling-to-interrogate-binding-affinity-in-neutralization-of-ricin-toxin-by-a-family-of-single-domain-antibodies
#1
Andrea Bazzoli, David J Vance, Michael J Rudolph, Yinghui Rong, Siva Krishna Angalakurthi, Ronald T Toth, C Russell Middaugh, David B Volkin, David D Weis, John Karanicolas, Nicholas J Mantis
In this report we investigated, within a group of closely related single domain camelid antibodies (VH Hs), the relationship between binding affinity and neutralizing activity as it pertains to ricin, a fast-acting toxin and biothreat agent. The V1C7-like VH Hs (V1C7, V2B9, V2E8, and V5C1) are similar in amino acid sequence, but differ in their binding affinities and toxin-neutralizing activities. Using the X-ray crystal structure of V1C7 in complex with ricin's enzymatic subunit (RTA) as a template, Rosetta-based homology modeling coupled with energetic decomposition led us to predict that a single pairwise interaction between Arg29 on V5C1 and Glu67 on RTA was responsible for the difference in ricin toxin binding affinity between V1C7, a weak neutralizer, and V5C1, a moderate neutralizer...
July 18, 2017: Proteins
https://www.readbyqxmd.com/read/28710264/two-novel-dissimilar-crystal-proteins-cry5ca1-and-cry5da1-synergistically-act-against-meloidogyne-incognita-and-delay-cry5ba-based-nematode-resistance
#2
Ce Geng, Yingying Liu, Miaomiao Li, Zhen Tang, Sajid Muhammad, Jinshui Zheng, Danfeng Wan, Donghai Peng, Lifang Ruan, Ming Sun
Cry proteins of Bacillus thuringiensis have been successfully used as biopesticides and transgenic crops throughout the world. However, resources against the most serious agricultural pathogens, plant root-knot nematodes, are limited. The genomes of several highly nematicidal virulent Bt strains from our laboratory have been sequenced, facilitating the identification of novel Cry proteins and other virulence factors. We identified two novel Cry proteins, Cry5Ca1 and Cry5Da1, that exhibit high toxicity against Meloidogyne incognita Using the Caenorhabditis elegans model, both Cry5 toxins showed to negatively affect nematode lifespan, fertility and survival...
July 14, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28705932/use-of-a-neutralizing-antibody-helps-identify-structural-features-critical-for-binding-of-clostridium-difficile-toxin-tcda-to-the-host-cell-surface
#3
Heather K Kroh, Ramyavardhanee Chandrasekaran, Kim Rosenthal, Rob Woods, Xiaofang Jin, Melanie D Ohi, Andrew C Nyborg, G Jonah Rainey, Paul Warrener, Benjamin W Spiller, D Borden Lacy
Clostridium difficile is a clinically significant pathogen that causes mild-to-severe (and often recurrent) colon infections. Disease symptoms stem from the activities of two large, multi-domain toxins known as TcdA and TcdB. The toxins can bind, enter, and perturb host cell function through a multi-step mechanism of receptor binding, endocytosis, pore formation, autoproteolysis, and glucosyltransferase-mediated modification of host substrates. Monoclonal antibodies that neutralize toxin activity provide a survival benefit in preclinical animal models and prevent recurrent infections in human clinical trials...
July 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28699724/toxicity-of-bacillus-thuringiensis-cry2ab-and-the-inheritance-of-cry2ab-resistance-in-the-pink-bollworm-pectinophora-gossypiella-saunders
#4
P A Malthankar, G T Gujar
Though the insecticidal crystal (Cry) proteins produced by Bacillus thuringiensis (Bt) are effective against insect pests, evolution of resistance remains an issue of great concern. Here, we explored the ability of pink bollworm, Pectinophora gossypiella (Lepidoptera: Gelechiidae), a key pest of cotton, to evolve resistance to Cry2Ab and characterized it in terms of inheritance. Sixteen day bioassay of Bt Cry2Ab toxin against 5-day old pink bollworm larvae showed median lethal concentration (LC(50)) ranging 0...
September 2016: Indian Journal of Experimental Biology
https://www.readbyqxmd.com/read/28650463/type-vi-secretion-tssk-baseplate-protein-exhibits-structural-similarity-with-phage-receptor-binding-proteins-and-evolved-to-bind-the-membrane-complex
#5
Van Son Nguyen, Laureen Logger, Silvia Spinelli, Pierre Legrand, Thi Thanh Huyen Pham, Thi Trang Nhung Trinh, Yassine Cherrak, Abdelrahim Zoued, Aline Desmyter, Eric Durand, Alain Roussel, Christine Kellenberger, Eric Cascales, Christian Cambillau
The type VI secretion system (T6SS) is a multiprotein machine widespread in Gram-negative bacteria that delivers toxins into both eukaryotic and prokaryotic cells. The mechanism of action of the T6SS is comparable to that of contractile myophages. The T6SS builds a tail-like structure made of an inner tube wrapped by a sheath, assembled under an extended conformation. Contraction of the sheath propels the inner tube towards the target cell. The T6SS tail is assembled on a platform-the baseplate-which is functionally similar to bacteriophage baseplates...
June 26, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28645943/the-structure-of-the-tetanus-toxin-reveals-ph-mediated-domain-dynamics
#6
Geoffrey Masuyer, Julian Conrad, Pål Stenmark
The tetanus neurotoxin (TeNT) is a highly potent toxin produced by Clostridium tetani that inhibits neurotransmission of inhibitory interneurons, causing spastic paralysis in the tetanus disease. TeNT differs from the other clostridial neurotoxins by its unique ability to target the central nervous system by retrograde axonal transport. The crystal structure of the tetanus toxin reveals a "closed" domain arrangement stabilised by two disulphide bridges, and the molecular details of the toxin's interaction with its polysaccharide receptor...
June 23, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28597156/molecular-characterization-of-indigenous-bacillus-thuringiensis-strains-isolated-from-kashmir-valley
#7
A L Reyaz, L Gunapriya, P Indra Arulselvi
Bacillus thuringiensis (Bt) being an eco-friendly bioinsecticide is effectively used in pest management strategies and, therefore, isolation and identification of new strains effective against a broad range of target pests is important. In the present study, new indigenous B. thuringiensis strains were isolated and investigated so that these could be used as an alternative and/or support the current commercial strains/cry proteins in use. For this, 159 samples including soil, leaf and spider webs were collected from ten districts of Kashmir valley (India)...
June 2017: 3 Biotech
https://www.readbyqxmd.com/read/28580925/crystal-structure-of-the-multiple-antibiotic-resistance-regulator-marr-from-clostridium-difficile
#8
J W Peng, H Yuan, X S Tan
Regulators of multiple antibiotic resistance (MarRs) are key players against toxins in prokaryotes. MarR homologues have been identified in many bacterial and archaeal species which pose daunting antibiotic resistance issues that threaten public health. The continuous prevalence of Clostridium difficile infection (CDI) throughout the world is associated with the abuse of antibiotics, and antibiotic treatments of CDI have limited effect. In the genome of C. difficile strain 630, the marR gene (ID 4913953) encodes a MarR protein...
June 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/28575388/functional-details-of-the-mycobacterium-tuberculosis-vapbc26-toxin-antitoxin-system-based-on-a-structural-study-insights-into-unique-binding-and-antibiotic-peptides
#9
Sung-Min Kang, Do-Hee Kim, Ki-Young Lee, Sung Jean Park, Hye-Jin Yoon, Sang Jae Lee, Hookang Im, Bong-Jin Lee
Toxin-antitoxin (TA) systems are essential for bacterial persistence under stressful conditions. In particular, Mycobacterium tuberculosis express VapBC TA genes that encode the stable VapC toxin and the labile VapB antitoxin. Under normal conditions, these proteins interact to form a non-toxic TA complex, but the toxin is activated by release from the antitoxin in response to unfavorable conditions. Here, we present the crystal structure of the M. tuberculosis VapBC26 complex and show that the VapC26 toxin contains a pilus retraction protein (PilT) N-terminal (PIN) domain that is essential for ribonuclease activity and that, the VapB26 antitoxin folds into a ribbon-helix-helix DNA-binding motif at the N-terminus...
May 31, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28562017/toxic-aromatics-induced-responsive-facets-for-a-pore-surface-functionalized-luminescent-coordination-polymer
#10
Biplab Manna, Shivani Sharma, Soumya Mukherjee, Aamod V Desai, Sujit K Ghosh
A luminescent coordination polymer was synthesized based on a linker prefunctionalization-based design principle coupled with an appropriate template selection protocol adopted during crystallization. Luminescent linker derived photoluminescence emission signature together with the reversibly dynamic host polymer exhibited a unique response toward environmentally toxic aromatics in the solid state, arguably crucial for the designed development of toxin-responsive solid materials.
May 31, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28539625/towards-new-cholera-prophylactics-and-treatment-crystal-structures-of-bacterial-enterotoxins-in-complex-with-gm1-mimics
#11
Julie Elisabeth Heggelund, Alasdair Mackenzie, Tobias Martinsen, Joel Benjamin Heim, Pavel Cheshev, Anna Bernardi, Ute Krengel
Cholera is a life-threatening disease in many countries, and new drugs are clearly needed. C-glycosidic antagonists may serve such a purpose. Here we report atomic-resolution crystal structures of three such compounds in complexes with the cholera toxin. The structures give unprecedented atomic details of the molecular interactions and show how the inhibitors efficiently block the GM1 binding site. These molecules are well suited for development into low-cost prophylactic drugs, due to their relatively easy synthesis and their resistance to glycolytic enzymes...
May 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28485498/plasmonic-nanoparticles-decorated-diatomite-biosilica-extending-the-horizon-of-on-chip-chromatography-and-label-free-biosensing
#12
Xianming Kong, Erwen Li, Kenny Squire, Ye Liu, Bo Wu, Li-Jing Cheng, Alan X Wang
Diatomite consists of fossilized remains of ancient diatoms and is a type of naturally abundant photonic crystal biosilica with multiple unique physical and chemical functionalities. In this paper, we explored the fluidic properties of diatomite as the matrix for on-chip chromatography and, simultaneously, the photonic crystal effects to enhance the plasmonic resonances of metallic nanoparticles for surface-enhanced Raman scattering (SERS) biosensing. The plasmonic nanoparticle-decorated diatomite biosilica provides a lab-on-a-chip capability to separate and detect small molecules from mixture samples with ultra-high detection sensitivity down to 1 ppm...
May 9, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/28481307/histopathological-effects-of-bt-and-tcda-insecticidal-proteins-on-the-midgut-epithelium-of-western-corn-rootworm-larvae-diabrotica-virgifera-virgifera
#13
Andrew J Bowling, Heather E Pence, Huarong Li, Sek Yee Tan, Steven L Evans, Kenneth E Narva
Western corn rootworm (WCR, Diabrotica virgifera virgifera LeConte) is a major corn pest in the United States, causing annual losses of over $1 billion. One approach to protect against crop loss by this insect is the use of transgenic corn hybrids expressing one or more crystal (Cry) proteins derived from Bacillus thuringiensis. Cry34Ab1 and Cry35Ab1 together comprise a binary insecticidal toxin with specific activity against WCR. These proteins have been developed as insect resistance traits in commercialized corn hybrids resistant to WCR feeding damage...
May 8, 2017: Toxins
https://www.readbyqxmd.com/read/28470711/carbohydrate-recognition-by-the-rhamnose-binding-lectin-sul-i-with-a-novel-three-domain-structure-isolated-from-the-venom-of-globiferous-pedicellariae-of-the-flower-sea-urchin-toxopneustes-pileolus
#14
Tomomitsu Hatakeyama, Ayaka Ichise, Hideaki Unno, Shuichiro Goda, Tatsuya Oda, Hiroaki Tateno, Jun Hirabayashi, Hitomi Sakai, Hideyuki Nakagawa
The globiferous pedicellariae of the venomous sea urchin Toxopneustes pileolus contains several biologically active proteins. We have cloned the cDNA of one of the toxin components, SUL-I, which is a rhamnose-binding lectin that acts as a mitogen through binding to carbohydrate chains on target cells. Recombinant SUL-I (rSUL-I) was produced in Escherichia coli cells, and its carbohydrate-binding specificity was examined with the glycoconjugate microarray analysis, which suggested that potential target carbohydrate structures are galactose-terminated N-glycans...
May 3, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28465678/protein-species-quantitative-venomics-looking-through-a-crystal-ball
#15
REVIEW
Juan J Calvete, Daniel Petras, Francisco Calderón-Celis, Bruno Lomonte, Jorge Ruiz Encinar, Alfredo Sanz-Medel
In this paper we discuss recent significant developments in the field of venom research, specifically the emergence of top-down proteomic applications that allow achieving compositional resolution at the level of the protein species present in the venom, and the absolute quantification of the venom proteins (the term "protein species" is used here to refer to all the different molecular forms in which a protein can be found. Please consult the special issue of Jornal of Proteomics "Towards deciphering proteomes via the proteoform, protein speciation, moonlighting and protein code concepts" published in 2016, vol...
2017: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/28462954/metal-organic-frameworks-functional-luminescent-and-photonic-materials-for-sensing-applications
#16
REVIEW
William P Lustig, Soumya Mukherjee, Nathan D Rudd, Aamod V Desai, Jing Li, Sujit K Ghosh
Metal-organic frameworks (MOFs) or porous coordination polymers (PCPs) are open, crystalline supramolecular coordination architectures with porous facets. These chemically tailorable framework materials are the subject of intense and expansive research, and are particularly relevant in the fields of sensory materials and device engineering. As the subfield of MOF-based sensing has developed, many diverse chemical functionalities have been carefully and rationally implanted into the coordination nanospace of MOF materials...
June 6, 2017: Chemical Society Reviews
https://www.readbyqxmd.com/read/28433497/clostridium-difficile-toxin-glucosyltransferase-domains-in-complex-with-a-non-hydrolyzable-udp-glucose-analogue
#17
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...
June 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
#18
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 commensal gut bacterial 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...
June 16, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28400471/a-novel-tarantula-toxin-stabilizes-the-deactivated-voltage-sensor-of-bacterial-sodium-channel
#19
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-of-yersinia-kristensenii-is-a-novel-bacterial-member-of-the-rnase-a-superfamily
#20
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...
May 19, 2017: Nucleic Acids Research
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