Structural vaccinology approach to investigate the virulent and secretory proteins of Bacillus anthracis for devising anthrax next-generation vaccine
01 Oct 2020-Journal of Biomolecular Structure & Dynamics (J Biomol Struct Dyn)-Vol. 38, Iss: 16, pp 4895-4905
TL;DR: Abstract Communicated by Ramaswamy H. Sarma is a post-graduate student of electrical engineering at the University of California, Berkeley and a member of the faculty at the California Institute of Technology, Berkeley.
Abstract: Abstract Communicated by Ramaswamy H. Sarma
Citations
More filters
TL;DR: A stable multivalent vaccine combining several T-cell and B-cell epitopes of the essential Nipah viral proteins with the help of different ligands and adjuvants which can effectively induce both humoral and cellular immune responses in human is designed.
Abstract: Nipah virus (NPV) is one of the most notorious viruses with a very high fatality rate. Because of the recurrent advent of this virus and its severe neurological implications, often leading to high ...
21 citations
TL;DR: The significance of the study deals with the identification of adjuvant (ligand) for human TLRs individually which assist in the development of the optimal highly immunogenic vaccine.
17 citations
TL;DR: The structural basis of the binding mechanism of 3-methyleneisoindolin-1-one molecules with ABA receptors is revealed and Mol26 and Mol25 were identified for the development of specific PYL3 agonists with a vast potential in agriculture to accentuate the ABA like action in plants.
16 citations
TL;DR: In this article, an immunoinformatic approach was employed to design a cross-immunogenic chimeric EiCh protein containing multi-epitopes, which is composed of 11 B-cell epitopes and 7 major histocompatibility complex class II epitopes identified from E.ictaluri immunogenic proteins previously reported.
Abstract: Edwardsiella ictaluri infects several fish species and protection of the all the susceptible fish hosts from the pathogen using a monovalent vaccine is impossible because the species is composed of host-based genotypes that are genetic, serological and antigenic heterogenous. Here, immunoinformatic approach was employed to design a cross-immunogenic chimeric EiCh protein containing multi-epitopes. The chimeric EiCh protein is composed of 11 B-cell epitopes and 7 major histocompatibility complex class II epitopes identified from E. ictaluri immunogenic proteins previously reported. The 49.32 kDa recombinant EiCh protein was expressed in vitro in Escherichia coli BL-21 (DE3) after which inclusion bodies were successfully solubilized and refolded. Ab initio protein modelling revealed secondary and tertiary structures. Secondary structure was confirmed by circular dichroism spectroscopy. Antigenicity of the chimeric EiCh protein was exhibited by strong reactivity with serum from striped catfish and Nile tilapia experimentally infected with E. ictaluri. Furthermore, immunogenicity of the chimeric EiCh protein was investigated in vivo in Nile tilapia juveniles and it was found that the protein could strongly induce production of specific antibodies conferring agglutination activity and partially protected Nile tilapia juveniles with a relative survival percentage (RPS) of 42%. This study explored immunoinformatics as reverse vaccinology approach in vaccine design for aquaculture to manage E. ictaluri infections.
8 citations
TL;DR: A preliminary phytochemical screening of the EtOH extract of the Pithecellobium dulce fruit peel showed the presence of alkaloids, glycosides, flavonoids, steroids, tannins, saponin and polyphenols.
Abstract: A preliminary phytochemical screening of the EtOH extract of the Pithecellobium dulce fruit peel showed the presence of alkaloids, glycosides, flavonoids, steroids, tannins, saponin and polyphenols. Notable amounts of phenolics and flavonoids were observed in the fruit peel extract. P. dulce fruit feel extract could potentially prevent the ROS damage and oxidative stress. The crude extract displayed higher DPPH (92.44%) and ABTS (94.51%) radical-scavenging activities. The GC–MS analysis of fruit peel extract revealed the presence of 36 bioactive compounds with pinitol, L-Rhamnose and 1, 5-anhydro-6-deoxyhexo-2, 3-diulose being the dominant compound and these might be responsible for the maximum radical-scavenging activities. Among these bioactive compounds, Pinitol was explored with the best drug-likeness properties with suitable pharmacokinetic properties. Docking and dynamics studies of GRP78-pinitol complex showed the minimized binding affinity (−6.8 kcal/mol) and exhibited the stable binding mode. The present results showed that the three lead compounds of P. dulce may act as noble inhibitors for GRP78 and the compounds can be re-designed and synthesized for potential anticancer activity.
6 citations
References
More filters
TL;DR: Details are given about protein identification and analysis software that is available through the ExPASy World Wide Web server and the extensive annotation available in the Swiss-Prot database is used.
Abstract: Protein identification and analysis software performs a central role in the investigation of proteins from two-dimensional (2-D) gels and mass spectrometry. For protein identification, the user matches certain empirically acquired information against a protein database to define a protein as already known or as novel. For protein analysis, information in protein databases can be used to predict certain properties about a protein, which can be useful for its empirical investigation. The two processes are thus complementary. Although there are numerous programs available for those applications, we have developed a set of original tools with a few main goals in mind. Specifically, these are: 1. To utilize the extensive annotation available in the Swiss-Prot database wherever possible, in particular the position-specific annotation in the Swiss-Prot feature tables to take into account posttranslational modifications and protein processing. 2. To develop tools specifically, but not exclusively, applicable to proteins prepared by two dimensional gel electrophoresis and peptide mass fingerprinting experiments. 3. To make all tools available on the World-Wide Web (WWW), and freely usable by the scientific community. In this chapter we give details about protein identification and analysis software that is available through the ExPASy World Wide Web server.
8,007 citations
TL;DR: Geometrical validation around the Cα is described, with a new Cβ measure and updated Ramachandran plot, and Favored and allowed ϕ,ψ regions are also defined for Pro, pre‐Pro, and Gly (important because Gly ϕ‐ψ angles are more permissive but less accurately determined).
Abstract: Geometrical validation around the Calpha is described, with a new Cbeta measure and updated Ramachandran plot. Deviation of the observed Cbeta atom from ideal position provides a single measure encapsulating the major structure-validation information contained in bond angle distortions. Cbeta deviation is sensitive to incompatibilities between sidechain and backbone caused by misfit conformations or inappropriate refinement restraints. A new phi,psi plot using density-dependent smoothing for 81,234 non-Gly, non-Pro, and non-prePro residues with B < 30 from 500 high-resolution proteins shows sharp boundaries at critical edges and clear delineation between large empty areas and regions that are allowed but disfavored. One such region is the gamma-turn conformation near +75 degrees,-60 degrees, counted as forbidden by common structure-validation programs; however, it occurs in well-ordered parts of good structures, it is overrepresented near functional sites, and strain is partly compensated by the gamma-turn H-bond. Favored and allowed phi,psi regions are also defined for Pro, pre-Pro, and Gly (important because Gly phi,psi angles are more permissive but less accurately determined). Details of these accurate empirical distributions are poorly predicted by previous theoretical calculations, including a region left of alpha-helix, which rates as favorable in energy yet rarely occurs. A proposed factor explaining this discrepancy is that crowding of the two-peptide NHs permits donating only a single H-bond. New calculations by Hu et al. [Proteins 2002 (this issue)] for Ala and Gly dipeptides, using mixed quantum mechanics and molecular mechanics, fit our nonrepetitive data in excellent detail. To run our geometrical evaluations on a user-uploaded file, see MOLPROBITY (http://kinemage.biochem.duke.edu) or RAMPAGE (http://www-cryst.bioc.cam.ac.uk/rampage).
3,963 citations
TL;DR: This protocol presents a community-wide web-based method using RaptorX (http://raptorx.uchicago.edu/) for protein secondary structure prediction, template-based tertiary structure modeling, alignment quality assessment and sophisticated probabilistic alignment sampling.
Abstract: A key challenge of modern biology is to uncover the functional role of the protein entities that compose cellular proteomes. To this end, the availability of reliable three-dimensional atomic models of proteins is often crucial. This protocol presents a community-wide web-based method using RaptorX (
http://raptorx.uchicago.edu/
) for protein secondary structure prediction, template-based tertiary structure modeling, alignment quality assessment and sophisticated probabilistic alignment sampling. RaptorX distinguishes itself from other servers by the quality of the alignment between a target sequence and one or multiple distantly related template proteins (especially those with sparse sequence profiles) and by a novel nonlinear scoring function and a probabilistic-consistency algorithm. Consequently, RaptorX delivers high-quality structural models for many targets with only remote templates. At present, it takes RaptorX ∼35 min to finish processing a sequence of 200 amino acids. Since its official release in August 2011, RaptorX has processed ∼6,000 sequences submitted by ∼1,600 users from around the world.
1,508 citations
TL;DR: Clinical presentation and course of cases of bioterrorism-related inhalational anthrax, in the District of Columbia, Florida, New Jersey, and New York, are described; survival of patients was markedly higher than previously reported.
Abstract: From October 4 to November 2, 2001, the first 10 confirmed cases of inhalational anthrax caused by intentional release of Bacillus anthracis were identified in the United States. Epidemiologic investigation indicated that the outbreak, in the District of Columbia, Florida, New Jersey, and New York, resulted from intentional delivery of B. anthracis spores through mailed letters or packages. We describe the clinical presentation and course of these cases of bioterrorism-related inhalational anthrax. The median age of patients was 56 years (range 43 to 73 years), 70% were male, and except for one, all were known or believed to have processed, handled, or received letters containing B. anthracis spores. The median incubation period from the time of exposure to onset of symptoms, when known (n=6), was 4 days (range 4 to 6 days). Symptoms at initial presentation included fever or chills (n=10), sweats (n=7), fatigue or malaise (n=10), minimal or nonproductive cough (n=9), dyspnea (n=8), and nausea or vomiting (n=9). The median white blood cell count was 9.8 X 10(3)/mm(3) (range 7.5 to 13.3), often with increased neutrophils and band forms. Nine patients had elevated serum transaminase levels, and six were hypoxic. All 10 patients had abnormal chest X-rays; abnormalities included infiltrates (n=7), pleural effusion (n=8), and mediastinal widening (seven patients). Computed tomography of the chest was performed on eight patients, and mediastinal lymphadenopathy was present in seven. With multidrug antibiotic regimens and supportive care, survival of patients (60%) was markedly higher (<15%) than previously reported.
928 citations
TL;DR: PEP-FOLD3 is a novel computational framework that allows both (i) de novo free or biased prediction for linear peptides between 5 and 50 amino acids, and (ii) the generation of native-like conformations of peptides interacting with a protein when the interaction site is known in advance.
Abstract: Structure determination of linear peptides of 5-50 amino acids in aqueous solution and interacting with proteins is a key aspect in structural biology. PEP-FOLD3 is a novel computational framework, that allows both (i) de novo free or biased prediction for linear peptides between 5 and 50 amino acids, and (ii) the generation of native-like conformations of peptides interacting with a protein when the interaction site is known in advance. PEP-FOLD3 is fast, and usually returns solutions in a few minutes. Testing PEP-FOLD3 on 56 peptides in aqueous solution led to experimental-like conformations for 80% of the targets. Using a benchmark of 61 peptide-protein targets starting from the unbound form of the protein receptor, PEP-FOLD3 was able to generate peptide poses deviating on average by 3.3A from the experimental conformation and return a native-like pose in the first 10 clusters for 52% of the targets. PEP-FOLD3 is available at http://bioserv.rpbs.univ-paris-diderot.fr/services/PEP-FOLD3.
627 citations