Research Topics
Genomes and Genes | Avigdor ShaffermanSummaryAffiliation: Israel Institute for Biological Research Country: Israel Publications
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Detail Information
Publications
Aging-resistant organophosphate bioscavenger based on polyethylene glycol-conjugated F338A human acetylcholinesteraseOhad Mazor
Israel Institute for Biological Research, Ness Ziona 74100, Israel
Mol Pharmacol 74:755-63. 2008....
Search for Bacillus anthracis potential vaccine candidates by a functional genomic-serologic screenOrit Gat
Israel Institute for Biological Research, P O Box 19, Ness Ziona 74100, Israel
Infect Immun 74:3987-4001. 2006..We list more than 30 novel B. anthracis immunoreactive virulence-related proteins which could be useful in diagnosis, pathogenesis studies, and future anthrax vaccine development...
Functional requirements for the optimal catalytic configuration of the AChE active centerAvigdor Shafferman
Department Biochemistry and Molecular Genetics, Israel Institute for Biological Research, P O Box 19, Ness Ziona 74100, Israel
Chem Biol Interact 157:123-31. 2005....
Genome-based bioinformatic selection of chromosomal Bacillus anthracis putative vaccine candidates coupled with proteomic identification of surface-associated antigensN Ariel
Israel Institute for Biological Research, Ness Ziona 74100, Israel
Infect Immun 71:4563-79. 2003..This study demonstrates that a combination of the bioinformatic and proteomic strategies may be useful in promoting the development of next generation anthrax vaccine...
Characterization of Bacillus anthracis iron-regulated surface determinant (Isd) proteins containing NEAT domainsOrit Gat
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel
Mol Microbiol 70:983-99. 2008..Studies with recombinant IsdK demonstrate specific binding to haemoglobin...
HtrA is a major virulence determinant of Bacillus anthracisTheodor Chitlaru
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona 74100, Israel
Mol Microbiol 81:1542-59. 2011..On a practical note, it is demonstrated that the attenuated Vollum ΔhtrA is highly efficacious in protecting guinea pigs against a lethal anthrax challenge...
Yersinia pestis endowed with increased cytotoxicity is avirulent in a bubonic plague model and induces rapid protection against pneumonic plagueAyelet Zauberman
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel
PLoS ONE 4:e5938. 2009..These observations have novel implications for the development of vaccines/therapies against Y. pestis and shed new light on the virulence strategies of Y. pestis in nature...
The NlpD lipoprotein is a novel Yersinia pestis virulence factor essential for the development of plagueAvital Tidhar
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel
PLoS ONE 4:e7023. 2009..Thus it could serve as a basis for a very potent live vaccine against bubonic and pneumonic plague...
T cells play an essential role in anti-F1 mediated rapid protection against bubonic plagueYinon Levy
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel
Vaccine 29:6866-73. 2011..These data extend our understanding of the immune mechanisms required for the development of a rapid and effective post-exposure therapy against plague...
Polyethylene-glycol conjugated recombinant human acetylcholinesterase serves as an efficacious bioscavenger against soman intoxicationChanoch Kronman
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona 74100, Israel
Toxicology 233:40-6. 2007....
Neutralization of Yersinia pestis-mediated macrophage cytotoxicity by anti-LcrV antibodies and its correlation with protective immunity in a mouse model of bubonic plagueAyelet Zauberman
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel
Vaccine 26:1616-25. 2008..The impact of overall findings on the potential use of serum neutralizing activity as a correlate of protective immunity is discussed...
A novel mechanism for antibody-based anthrax toxin neutralization: inhibition of prepore-to-pore conversionAdva Mechaly
Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona 74100, Israel
J Biol Chem 287:32665-73. 2012..In conclusion, these experiments demonstrate that cAb29 exerts its potent neutralizing activity in a unique manner by blocking the prepore-to-pore conversion process...
Is aromaticity essential for trapping the catalytic histidine 447 in human acetylcholinesterase?Dana Kaplan
Department of Biochemistry and Molecular Biology, Israel Institute for Biological Research, Ness Ziona 74100, Israel
Biochemistry 43:3129-36. 2004..The results also underscore the role of the acyl pocket subsite of cholinesterases in maintaining the catalytically viable conformation of the catalytic histidine...
Identification of chromosomally encoded membranal polypeptides of Bacillus anthracis by a proteomic analysis: prevalence of proteins containing S-layer homology domainsTheodor Chitlaru
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel
Proteomics 4:677-91. 2004....
Interaction of Yersinia pestis with macrophages: limitations in YopJ-dependent apoptosisAyelet Zauberman
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, P.O. Box 19, Ness-Ziona, 74100, Israel
Infect Immun 74:3239-50. 2006..enterocolitica WA O:8. We suggest that the relative inferiority of Y. pestis in triggering cell death in macrophages may be advantageous for its in vivo propagation in the early stages of infection...
The solute-binding component of a putative Mn(II) ABC transporter (MntA) is a novel Bacillus anthracis virulence determinantOrit Gat
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, PO Box 19, Ness Ziona, 74100, Israel
Mol Microbiol 58:533-51. 2005..We propose that MntA is a novel B. anthracis virulence determinant essential for the development of anthrax disease, and that B. anthracisDeltamntA strains have the potential to serve as platform for future live attenuated vaccines...
Next generation OP-bioscavengers: a circulatory long-lived 4-PEG hypolysine mutant of F338A-HuAChE with optimal pharmacokinetics and pseudo-catalytic characteristicsChanoch Kronman
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, 24 Rueven St, P O Box 19, Ness Ziona 74100, Israel
Chem Biol Interact 187:253-8. 2010..This selected 4-PEG F338A-AChE can serve as a paradigm for new generation OP-bioscavengers, specifically tailored for prophylactic treatment against toxic OP-agents...
Differential contribution of Bacillus anthracis toxins to pathogenicity in two animal modelsHaim Levy
Department of Infectious Diseases, Israel Institute for Biological Research, Ness Ziona, Israel
Infect Immun 80:2623-31. 2012..anthracis virulence in general and in particular for the design of relevant next-generation anthrax vaccines...
Controlled concealment of exposed clearance and immunogenic domains by site-specific polyethylene glycol attachment to acetylcholinesterase hypolysine mutantsOfer Cohen
Department of Biochemistry, Israel Institute for Biological Research, Ness Ziona 74100, Israel
J Biol Chem 282:35491-501. 2007....
Accommodation of physostigmine and its analogues by acetylcholinesterase is dominated by hydrophobic interactionsDov Barak
Israel Institute for Biological Research, Ness Ziona 74100, Israel
Biochem J 417:213-22. 2009..The present study demonstrates that certain charged and uncharged ligands, like analogues of physostigmine and physovenine, seem to be accommodated by the enzyme mostly through hydrophobic interactions...
Flexibility versus "rigidity" of the functional architecture of AChE active centerAvigdor Shafferman
Department Biochemistry and Molecular Biology, Israel Institute for Biological Research, Ness Ziona, Israel
Chem Biol Interact 175:166-72. 2008..These studies suggest that the combination of "rigidity" and flexibility within the HuAChE gorge are an essential element of its molecular design...
In vitro screen of bioinformatically selected Bacillus anthracis vaccine candidates by coupled transcription, translation, and immunoprecipitation analysisOrit Gat
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel
Methods Mol Biol 375:211-33. 2007..Protocols will be provided for application of these methods to analyze the anti-B. anthracis antibody repertoire of hyperimmune sera or sera from convalescent and from DNA-vaccinated animals...
Discordance in the effects of Yersinia pestis on the dendritic cell functions manifested by induction of maturation and paralysis of migrationBaruch Velan
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, P O Box 19, Ness Ziona 74100, Israel
Infect Immun 74:6365-76. 2006..pestis harboring the plasmid failed to do so. Taken together, these results suggest that virulence plasmid-dependent impairment of DC migration is the major mechanism utilized by Y. pestis to subvert DC function...
Comparison of polyethylene glycol-conjugated recombinant human acetylcholinesterase and serum human butyrylcholinesterase as bioscavengers of organophosphate compoundsOfer Cohen
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel
Mol Pharmacol 70:1121-31. 2006..3-1.5 LD50). These findings together with the observations that the PEGylated rHuAChE exhibits unaltered biodistribution and high bioavailability present a case for using PEGylated rHuAChE as a very efficacious bioscavenger of OP agents...
Progress and novel strategies in vaccine development and treatment of anthraxTheodor Chitlaru
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel
Immunol Rev 239:221-36. 2011....
Lessons from functional analysis of AChE covalent and noncovalent inhibitors for design of AD therapeutic agentsDov Barak
Department of Organic Chemistry, Israel Institute for Biological Research, P.O. Box 19, Ness-Ziona 74100, Israel
Chem Biol Interact 157:219-26. 2005..Thus, elucidation of the functional architecture of the HuAChE active center is bound to be of considerable utility in the current effort to design novel covalent AChE inhibitors as therapeutics for Alzheimer's disease (AD)...
Amino acid domains control the circulatory residence time of primate acetylcholinesterases in rhesus macaques (Macaca mulatta)Ofer Cohen
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona 74100, Israel
Biochem J 378:117-28. 2004..This extended residence time is similar to that displayed by native macaque butyrylcholinesterase (9950 min), which is the prevalent cholinesterase form in the circulation of adult macaques...
Effects of spontaneous deamidation on the cytotoxic activity of the Bacillus anthracis protective antigenGil Zomber
Department of Biotechnology, Israel Institute for Biological Research, Ness Ziona 74100, Israel
J Biol Chem 280:39897-906. 2005..We suggest that PA inactivation during storage is associated with susceptible deamidation sites, which are intimately involved in both mechanisms of PA cleavage by furin and PA-receptor binding...
A single cidofovir treatment rescues animals at progressive stages of lethal orthopoxvirus diseaseTomer Israely
Israel Institute for Biological Research, Ness Ziona, Israel
Virol J 9:119. 2012..e. either alone or in conjunction with active vaccination, can rescue ECTV infected mice...
Clusters versus affinity-based approaches in F. tularensis whole genome search of CTL epitopesAnat Zvi
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel
PLoS ONE 7:e36440. 2012..tularensis dataset of known CTL epitopes. The generality and power of the high density cluster-based approach suggest that it can be a valuable tool for identification of novel CTLs in proteomes of other bacterial pathogens...
Identification of in vivo-expressed immunogenic proteins by serological proteome analysis of the Bacillus anthracis secretomeTheodor Chitlaru
Israel Institute for Biological Research, P O Box 19, Ness Ziona 74100, Israel
Infect Immun 75:2841-52. 2007..anthracis strain Vollum spores...
Host-regulated disposition of mammalian AChEsChanoch Kronman
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel
Chem Biol Interact 157:51-5. 2005....
The aromatic "trapping" of the catalytic histidine is essential for efficient catalysis in acetylcholinesteraseDov Barak
Department of Organic Chemistry, Israel Institute for Biological Research, Ness Ziona, 74100, Israel
Biochemistry 41:8245-52. 2002....
Proteomic studies of Bacillus anthracisTheodor Chitlaru
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona 74100, Israel
Future Microbiol 4:983-98. 2009..anthracis protein targets for further evaluation in detection, diagnostics, therapy and prophylaxis, and contributed to the elucidation of some aspects of the pathogenesis of the disease...
Generation of Yersinia pestis attenuated strains by signature-tagged mutagenesis in search of novel vaccine candidatesYehuda Flashner
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, 74100, Israel
Infect Immun 72:908-15. 2004..This Kimberley53pcm mutant was superior to the EV76 live vaccine strain because it induced 10- to 100-fold-higher antibody titers to the protective V and F1 antigens and because it conferred efficacious protective immunity...
Consequences of delayed ciprofloxacin and doxycycline treatment regimens against Francisella tularensis airway infectionShahar Rotem
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel
Antimicrob Agents Chemother 56:5406-8. 2012..A delay in onset of both antibiotic treatments allowed the rescue of all LVS-infected animals. However, for animals infected with SchuS4, only ciprofloxacin was efficacious and prolongation of treatment rescued all animals...
The role of AChE active site gorge in determining stereoselectivity of charged and noncharged VX enantiomersArie Ordentlich
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel
Chem Biol Interact 157:191-8. 2005..Such different orientations of the charged leaving group in the HuAChE adducts of the VX enantiomers seem to be a consequence of intramolecular interactions with the bulky phosphorus alkoxy group...
Interrelationship between dendritic cell trafficking and Francisella tularensis dissemination following airway infectionErez Bar-Haim
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel
PLoS Pathog 4:e1000211. 2008..tularensis in the early stages of infection, and that DC trafficking plays a role in pathogen dissemination. This underscores the therapeutic potential of DC migration impairing drugs in tularemia treatment...
Contribution of immunological memory to protective immunity conferred by a Bacillus anthracis protective antigen-based vaccineHadar Marcus
Department of Biotechnology, Israel Institute for Biological Research, 74100 Ness-Ziona, Israel
Infect Immun 72:3471-7. 2004..Therefore, to allow for the establishment of memory-dependent protection prior to the expected onset of disease, booster immunizations should not be used without concomitant antimicrobial treatment in postexposure scenarios...
Identification and characterization of novel and potent transcription promoters of Francisella tularensisGalia Zaide
Israel Institute for Biological Research, P O Box 19, Ness Ziona 74100, Israel
Appl Environ Microbiol 77:1608-18. 2011..tularensis intended to gain better understanding of the mechanisms involved in pathogenesis and virulence, as well as for vaccine development studies...
Effective protective immunity to Yersinia pestis infection conferred by DNA vaccine coding for derivatives of the F1 capsular antigenHaim Grosfeld
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona 74100, Israel
Infect Immun 71:374-83. 2003..Taken together, these observations indicate that a tailored genetic vaccine based on a bacterial protein can be used to confer protection against plague in mice without resorting to regimens involving the use of purified proteins...
Whole-genome immunoinformatic analysis of F. tularensis: predicted CTL epitopes clustered in hotspots are prone to elicit a T-cell responseAnat Zvi
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona, Israel
PLoS ONE 6:e20050. 2011..tularensis, could be applied in immunoinformatic analyses of many other complex pathogen genomes...
Effective post-exposure protection against lethal orthopoxviruses infection by vaccinia immune globulin involves induction of adaptive immune responseShlomo Lustig
Department of Infectious Diseases, Israel Institute for Biological Research, Israel
Vaccine 27:1691-9. 2009..Vaccine efficiency is not impaired, providing a non-prohibitive VIG dose is used. Thus, VIG can be used as a prophylactic measure against post-vaccinal complications but could also serve for post-exposure treatment against smallpox...
Postexposure immunization with modified vaccinia virus Ankara or conventional Lister vaccine provides solid protection in a murine model of human smallpoxNir Paran
Israel Institute for Biological Research, Ness Ziona, Israel
J Infect Dis 199:39-48. 2009..Scenarios of sudden biothreats have prompted demand for rapidly protective vaccination. However, the feasibility of short-term vaccination (i.e., vaccination shortly before exposure) with vaccinia virus (VACV) is uncertain...
Overloading and removal of N-glycosylation targets on human acetylcholinesterase: effects on glycan composition and circulatory residence timeTheodor Chitlaru
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, 74100, Israel
Biochem J 363:619-31. 2002..This study provides evidence that glycan loading, together with N-glycan terminal processing and enzyme subunit oligomerization, operate in a hierarchical and concerted manner in determining the pharmacokinetic characteristics of AChE...
Disparity between Yersinia pestis and Yersinia enterocolitica O:8 in YopJ/YopP-dependent functionsAyelet Zauberman
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness Ziona
Adv Exp Med Biol 603:312-20. 2007..pestis and Y. enterocolitica O:8 virulent strains shows some critical disparity in YopJ/YopP-related effects on immune cells. Involvement of yopJ in virulence was evaluated in mouse model of bubonic plague...
Construction of a rhamnose mutation in Bacillus anthracis affects adherence to macrophages but not virulence in guinea pigsJoel A Bozue
Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, USAMRIID, Ft Detrick, MD 21702, USA
Microb Pathog 38:1-12. 2005..These results suggest that the incorporation of rhamnose into the spore coat of B. anthracis is required for optimal interaction with macrophages but is not required for full virulence in this animal model...
Vaccination with plasmid DNA expressing the Yersinia pestis capsular protein F1 protects mice against plagueHaim Grosfeld
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, P.O. Box 19, Ness-Ziona, Israel 74100
Adv Exp Med Biol 529:423-4. 2003
The NheA component of the non-hemolytic enterotoxin of Bacillus cereus is produced by Bacillus anthracis but is not required for virulenceItai Mendelson
United States Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Fort Detrick, Frederick, MD 21702, USA
Microb Pathog 37:149-54. 2004..anthracis produces and secretes the NheA subunit of NHE. A NheA deletion mutant was not attenuated in the guinea pig suggesting that NheA is not absolutely required for virulence...
Evaluation of protective immunity induced by Yersinia enterocolitica type-III secretion system mutantsEmanuelle Mamroud
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, P.O. Box 19, Ness-Ziona, Israel 74100
Adv Exp Med Biol 529:425-30. 2003
Differential proteomic analysis of the Bacillus anthracis secretome: distinct plasmid and chromosome CO2-dependent cross talk mechanisms modulate extracellular proteolytic activitiesTheodor Chitlaru
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona
J Bacteriol 188:3551-71. 2006....
Pressure and heat inactivation of recombinant human acetylcholinesterase. Importance of residue E202 for enzyme stabilityCécile Cléry-Barraud
Centre de Recherches du Service de Sante des Armees, Unite d Enzymologie, France
Eur J Biochem 269:4297-307. 2002..In conclusion, pressure and thermal stability of mutants provided evidence that the residue E202 is a determinant of structural and functional stability of HuAChE...
Stereoselectivity toward VX is determined by interactions with residues of the acyl pocket as well as of the peripheral anionic site of AChEArie Ordentlich
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, 74100 Israel
Biochemistry 43:11255-65. 2004..The results from kinetic studies and molecular simulations suggest that the differential reactivity toward the VX enantiomers is mainly a result of a different interaction of the charged leaving group with Asp74...
Identification of genes involved in Yersinia pestis virulence by signature-tagged mutagenesisYehuda Flashner
Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, P.O. Box 19, Ness-Ziona, Israel 74100
Adv Exp Med Biol 529:31-3. 2003
Inhibition of human acetyl- and butyrylcholinesterase by novel carbamates of (-)- and (+)-tetrahydrofurobenzofuran and methanobenzodioxepineWeiming Luo
Drug Design and Development Section, Laboratory of Neurosciences, Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, Maryland 21224, USA
J Med Chem 49:2174-85. 2006....
