A5023328167- Toxin Mechanisms and Immunotoxins
- Bacterial Genetics and Biotechnology
- Lipid Membrane Structure and Behavior
- PARP inhibition in cancer therapy
- RNA and protein synthesis mechanisms
- Antimicrobial Resistance in Staphylococcus
- Protein Structure and Dynamics
- Antimicrobial Peptides and Activities
- Vibrio bacteria research studies
- Calcium signaling and nucleotide metabolism
- Clostridium difficile and Clostridium perfringens research
- Insect and Pesticide Research
- Cancer therapeutics and mechanisms
- Biochemical and Structural Characterization
- Mass Spectrometry Techniques and Applications
- Transgenic Plants and Applications
- Ion channel regulation and function
- GABA and Rice Research
- CRISPR and Genetic Engineering
- Clinical Nutrition and Gastroenterology
- Plant and animal studies
- Bacillus and Francisella bacterial research
- Photoreceptor and optogenetics research
- Pancreatic function and diabetes
- Escherichia coli research studies
University of Guelph
2014-2023
State University of New York
2007
University of Windsor
1997
Purdue University West Lafayette
1988-1993
Yamaguchi University
1993
Boston University
1991
University of Ottawa
1986-1987
The ADP-ribosyltransferases are a class of enzymes that display activity in variety bacterial pathogens responsible for causing diseases plants and animals, including those affecting mankind, such as diphtheria, cholera, whooping cough. We report the characterization novel toxin from Vibrio cholerae, which we call cholix toxin. is active against mammalian cells (IC50 = 4.6 ± 0.4 ng/ml) crustaceans (Artemia nauplii LD50 10 2 μg/ml). Here show this third member diphthamide-specific ADP-ribose...
The surface of a gold electrode was functionalized with hydrophilic monolayer 1-thio-β-D-glucose formed by spontaneous self-assembly. Langmuir-Blodgett/Langmuir-Schaefer (LB/LS) method then used to assemble bilayer onto the modified Au(111) surface. lipid membrane (BLM) separated from incorporating monosialoganglioside GM1 into inner leaflet composed 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol. To make leaflet, monolayers GM1/DMPC/cholesterol mole ratios 1:6:3, 2:5:3,...
A bioinformatics strategy was used to identify Scabin, a novel DNA-targeting enzyme from the plant pathogen 87.22 strain of Streptomyces scabies. Scabin shares nearly 40% sequence identity with Pierisin family mono-ADP-ribosyltransferase toxins. purified homogeneity as 22-kDa single-domain and shown possess high NAD+-glycohydrolase (Km(NAD) = 68 ± 3 μm; kcat 94 2 min−1) activity an RSQXE motif; it also target deoxyguanosine showed sigmoidal kinetics (K0.5(deoxyguanosine) 302 12 14 min−1)....
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIdentification of a voltage-responsive segment the potential-gated colicin E1 ion channelA. R. Merrill and William A. CramerCite this: Biochemistry 1990, 29, 37, 8529–8534Publication Date (Print):September 18, 1990Publication History Published online1 May 2002Published inissue 18 September 1990https://pubs.acs.org/doi/10.1021/bi00489a004https://doi.org/10.1021/bi00489a004research-articleACS PublicationsRequest reuse permissionsArticle...
Chelt, a cholera-like toxin from Vibrio cholerae, and Certhrax, an anthrax-like Bacillus cereus, are among six new bacterial protein toxins we identified characterized using in silico cell-based techniques. We also uncovered medically relevant Mycobacterium avium Enterococcus faecalis. found agriculturally Photorhabdus luminescens splendidus. These belong to the ADP-ribosyltransferase family that has conserved structure despite low sequence identity. Therefore, our search for combined fold...
C3larvin toxin was identified by a bioinformatic strategy as putative mono-ADP-ribosyltransferase and possible virulence factor from Paenibacillus larvae, which is the causative agent of American Foulbrood in honey bees. targets RhoA substrate for its transferase reaction, kinetics both NAD+ (Km = 34 ± 12 μm) 17 3 substrates were characterized this enzyme C3 subgroup. toxic to yeast when expressed cytoplasm, catalytic variants lost ability kill host, indicating that exerts lethality through...
Chronocoulometry and photon polarisation modulation infrared reflection absorption spectroscopy (PM-IRRAS) have been employed to study the fusion of dimyristoylphosphatidylcholine (DMPC) vesicles onto a Au(111) electrode surface. The results show that is controlled by potential or charge at surface (sigmaM). At densities -15 microC cm(-2) < sigmaM 0 cm(-2), DMPC fuse form condensed film. When de-wetting film from occurs. detached surface; however, phospholipid molecules remain in its close...
The structure of the membrane bound state 178-residue thermolytic COOH-terminal channel forming peptide colicin El was studied by polarized Fourier transform infrared (FTIR) spectroscopy.This fragment reconstituted into DMPC liposomes at varying peptide/lipid ratios ranging from 1/25-1/500.The amide I band frequency protein indicated a dominant a-helical secondary with limited 1-and random structures.The and 11 frequencies are 1,656 1,546 cm-', close to bands rhodopsin, bacteriorhodopsin...
Constitutive expression of an Arabidopsis thaliana (L.) Heynh cDNA (GenBank accession No. AY044183 ) in a succinic semialdehyde (SSA) dehydrogenase-deficient yeast ( Saccharomyces cerevisiae Hansen) mutant enables growth on γ-aminobutyrate and significantly enhances the accumulation γ-hydroxybutyrate. In this report, (designated hereinafter as AtGR1) was functionally expressed Escherichia coli , recombinant protein purified to homogeneity. Kinetic analysis substrate specificity revealed that...
Photorhabdus luminescens is a pathogenic bacterium that produces many toxic proteins. The mono-ADP-ribosyltransferases (mARTs) are an enzyme class produced by numerous bacteria and participate in disease plants animals, including humans. Herein we report novel mART from P. called Photox. This 46-kDa toxin shows high homology to other actin-targeting mARTs hallmark catalytic regions similar core fold. Furthermore, Photox vivo cytotoxic activity against yeast, with protection occurring when...
The mono-ADPRT (mono-ADP-ribosyltransferase), Pseudomonas aeruginosa ETA (exotoxin A), catalyses the transfer of ADP-ribose from NAD+ to its protein substrate. A series water-soluble compounds that structurally mimic nicotinamide moiety was investigated for their inhibition catalytic domain ETA. importance an amide locked into a hetero-ring structure and core system is planar trend evident by IC50 values. Also, weaker inhibitors have ring structures are less thus more flexible. One most...
Various bacterial pathogens secrete toxins, which are not only responsible for fatal pathogenesis of disease, but also facilitate evasion host defences. One the best-known toxin groups is mono-ADP-ribosyltransferase family. In present study, we demonstrate that human neutrophil α-defensins potent inhibitors enzymes, particularly against DT (diphtheria toxin) and ETA (Pseudomonas exotoxin A). HNP1 (human protein 1) inhibited DT- or ETA-mediated ADP-ribosylation eEF2 (eukaryotic elongation...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAcrylamide quenching of the intrinsic fluorescence tryptophan residues genetically engineered into soluble colicin E1 channel peptide. Structural characterization insertion-competent stateA. R. Merrill, L. Palmer, and A. G. SzaboCite this: Biochemistry 1993, 32, 27, 6974–6981Publication Date (Print):July 1, 1993Publication History Published online1 May 2002Published inissue 1 July 1993https://doi.org/10.1021/bi00078a023RIGHTS & PERMISSIONSArticle...
The mono-ADP-ribosyltransferase toxins are bacterial virulence factors that contribute to many disease states in plants, animals, and humans. These function as enzymes target various host proteins covalently attach an ADP-ribose moiety alters protein function. We tested compounds from a virtual screen of commercially available combined with directed poly(ADP-ribose) polymerase (PARP) inhibitor library found several bind tightly inhibit Pseudomonas aeruginosa Vibrio cholerae. most efficacious...
The molecular nature of the protein-protein interactions between catalytic domain from Pseudomonas aeruginosa exotoxin A (PE24H) and its protein substrate, eukaryotic elongation factor-2 (eEF-2) were probed using a fluorescence resonance energy transfer method. Single cysteine mutant proteins PE24H prepared site-specifically labeled with donor fluorophore IAEDANS (5-(2-iodoacetylaminoethylamino)-1-napthalenesulfonic acid), whereas eEF-2 was acceptor fluorescein. association found to be...
Pseudomonas aeruginosa produces the virulence factor, ETA (exotoxin A), which catalyses an ADP-ribosyltransferase reaction of its target protein, eEF2 (eukaryotic elongation factor-2). Currently, this protein–protein interaction is poorly characterized and study was aimed at identifying contact sites between catalytic domain (PE24H, from P. aeruginosa, a 24 kDa C-terminal fragment containing His6 tag). Single-cysteine residues were introduced into toxin 21 defined surface-exposed labelled...
The emergence of bacterial antibiotic resistance poses a significant challenge in the pursuit novel therapeutics, making new strategies for drug discovery imperative. We have developed yeast growth-defect phenotypic screen to help solve this current dilemma. This approach facilitates identification and characterization diphtheria toxin (DT) group, ADP-ribosyltransferase toxins from pathogenic bacteria. In addition, assay utilizes Saccharomyces cerevisiae, reliable model expression,...