A5034810100- Toxin Mechanisms and Immunotoxins
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Transgenic Plants and Applications
- Antimicrobial Peptides and Activities
- Lipid Membrane Structure and Behavior
- Glycosylation and Glycoproteins Research
- Bacterial Genetics and Biotechnology
- Biochemical and Structural Characterization
- Clostridium difficile and Clostridium perfringens research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- SARS-CoV-2 and COVID-19 Research
- CAR-T cell therapy research
- Immune cells in cancer
- Microbial Inactivation Methods
- COVID-19 Clinical Research Studies
- T-cell and B-cell Immunology
- Bacterial Infections and Vaccines
- S100 Proteins and Annexins
- Plant tissue culture and regeneration
- Immune Cell Function and Interaction
- Antibiotics Pharmacokinetics and Efficacy
- Antibiotic Resistance in Bacteria
- PARP inhibition in cancer therapy
- Probiotics and Fermented Foods
IGM Biosciences (United States)
2020-2024
Lypro Biosciences (United States)
2013
Trellis Bioscience (United States)
2009
Altair Engineering (United States)
2007
XOMA (United States)
1994-2003
University of California, Los Angeles
1979-1997
The University of Texas Southwestern Medical Center
1997
Sonoma Technology (United States)
1992-1994
University of Minnesota
1991-1992
Fairview Health Services
1992
Plasma endotoxin and lipopolysaccharide-binding protein (LBP) levels were measured in a group of 253 patients at the onset severe sepsis and/or septic shock. Endotoxin significantly greater than control (n = 33; mean ± SD, 5.1 7.3, pg/mL) 78.3% patients. Median with 300 pg/mL (25%–75% interquartile range, 110–726 pg/mL). LBP elevated 97% compared normal values 4.1 1.65 µg/mL. 31.2 µg/mL (interquartile 22.5–47.7 µg/mL). study entry more highly (515 vs. 230 pg/mL; P < .01), less (28.0 33.2...
Exotoxin A of Pseudomonas aeruginosa is a secreted bacterial toxin capable translocating catalytic domain into mammalian cells and inhibiting protein synthesis by the ADP-ribosylation cellular elongation factor 2. The single polypeptide chain 613 amino acids. x-ray crystallographic structure exotoxin A, determined to 3.0-A resolution, shows following: an amino-terminal domain, composed primarily antiparallel beta-structure comprising approximately half molecule; middle alpha-helices;...
Bactericidal/permeability-increasing protein (BPI), a potent antimicrobial of 456 residues, binds to and neutralizes lipopolysaccharides from the outer membrane Gram-negative bacteria. At resolution 2.4 angstroms, crystal structure human BPI shows boomerang-shaped molecule formed by two similar domains. Two apolar pockets on concave surface boomerang each bind phosphatidylcholine, primarily interacting with their acyl chains; this suggests that may also chains lipopolysaccharide. As model...
ABSTRACT The lipopolysaccharide (LPS)-binding protein (LBP) has a concentration-dependent dual role in the pathogenesis of gram-negative sepsis: low concentrations LBP enhance LPS-induced activation mononuclear cells (MNC), whereas acute-phase rise inhibits cellular stimulation. In stimulation experiments, we have found that mediates cytokine release from MNC even under serum-free conditions. biophysical experiments demonstrated binds and intercalates into lipid membranes, amplified by...
Photoaffinity labeling with native NAD, a method employed earlier diphtheria toxin (DT), was used to identify an active site residue of Pseudomonas aeruginosa exotoxin A (ETA). An enzymically fragment (Mr 27,000), derived by partial digestion ETA thermolysin, irradiated ultraviolet light (254 nm) in the presence various radiolabeled preparations NAD. Label from nicotinamide moiety efficiently transferred protein (maximally 0.79 mol/mol), and label exclusively located at position 553. This...
Objective. The mechanisms by which newborns are at increased risk for invasive bacterial infections have been incompletely defined. A central element of innate immunity to infection is the neutrophil—a cell that contains cytoplasmic granules replete with antibiotic proteins and peptides. activity adult neutrophils against Gram-negative bacteria believed depend a significant degree on presence in neutrophil primary (azurophilic) 55-kDa bactericidal/permeability-increasing protein (BPI), binds...
We showed earlier that exposing mixtures of NAD and diphtheria toxin fragment A to ultraviolet radiation (253.7 nm) induced the formation covalently linked protein-ligand photoproducts. Here we report when [carbonyl-14C]NAD was employed in such procedures, efficiency labeling protein approached 1 mol/mol, at least 94% incorporated label associated with a single residue, glutamic acid position 148. Fragment photolabeled this manner enzymically inactive. The photolabeling much lower (less than...
Abstract The activation of cells by endotoxin (LPS) is one the early host responses to infections with Gram-negative bacteria. lipid A part LPS molecules known represent endotoxic principle; however, specific requirements for expression biologic activity are still not fully understood. We previously found that a molecular conformation (endotoxic conformation) prerequisite be biologically active. In this study, we have investigated interdependence charge and natural chemically modified its...
Abstract Two related mammalian proteins, bactericidal/permeability‐increasing protein (BPI) and lipopolysaccharide‐binding (LBP), share high‐affinity binding to lipopolysaccharide (LPS), a glycolipid found in the outer membrane of Gram‐negative bacteria. The recently determined crystal structure human BPI permits structure/function analysis, presented here, conserved regions these two proteins sequences. In seven known sequences LBP, 102 residues are completely may be classified terms...
Native human Abs represent attractive drug candidates; however, the low frequency of B cells expressing high-quality has posed a barrier to discovery. Using novel single-cell phenotyping technology, we have overcome this discover targeting conserved but poorly immunogenic central motif respiratory syncytial virus (RSV) G protein. For entire cohort 24 subjects with recent RSV infection, producing meeting these stringent specificity criteria were rare, <10 per million. Several newly cloned...
Lipopolysaccharides (LPS, endotoxin) stimulate mononuclear cells to release cytokines which initiate endotoxic effects. Interaction of LPS at low concentrations with target is CD14‐independent whereas high it CD14‐independent. Here, we demonstrate by resonance energy transfer (RET) technique that nonspecific, intercalation into membrane systems can be mediated lipopolysaccharide‐binding protein (LBP). It proposed in this pathway, LBP breaks down aggregates, transports the smaller units and...
Manipulation of infection calculi (struvite and calcium apatite) can cause the sepsis syndrome due to endotoxemia or bacteremia. We sought determine whether concentrations endotoxin sufficient produce could be embedded in renal stones.Fragments noninfection were processed assayed for concentration. Endotoxin concentrations, recorded as units per gm. calculus, converted ng. (10 = 1 ng.). Urine culture results available some patients with stones.A total 34 (16 18 noninfection) evaluated. The...
Irradiation of mixtures diphtheria toxin fragment A and [carbonyl-14C]NAD with UV light (253.7 nm) is known to induce efficient transfer the radiolabel position 148, corresponding glutamic acid in unmodified protein. Here we report structure photoproduct at as determined by chemical photochemical methods, fast-atom-bombardment mass spectrometry, nuclear magnetic resonance. The [an alpha-amino-gamma-(6-nicotin-amidyl)butyric residue] contains entire nicotinamide moiety NAD linked via its...
Lipopolysaccharide (LPS)-binding protein (LBP) and bactericidal/permeability-increasing (BPI) are two structurally related lipid A-binding proteins with divergent functional activities. LBP mediates activation of macrophage other proinflammatory cells. In contrast, BPI has potent bactericidal LPS-neutralizing A recombinant fragment (rBPI23) retains the biological activities holo may represent a novel therapeutic agent for treatment gram-negative infections, sepsis, endotoxemia. For...
Abstract LPS-binding protein (LBP) mediates the pro-inflammatory effects of bacterial LPS by enhancing LPS-induced cytokine production monocytic cells. LBP binds specifically to generate a complex that interacts with CD14 receptor on surface responsive To identify biologically active regions responsible for mediating these activities, we cloned and expressed human rLBP (456 amino acids) as well truncated form encoding acids 1-197 (rLBP25). Both forms bound same affinity, similarly inhibited...
Several metabolic parameters indicative of Escherichia coli function and integrity were kinetically examined in response to treatment with normal human serum the presence absence functional lysozyme. Specific inhibition this enzyme bacteriolytic bactericidal reactions was accomplished by using purified rabbit anti-human lysozyme immunoglobulin G. Initiation complement-mediated alterations cytoplasmic membrane integrity, as judged leakage 86Rb from prelabeled cells or hydrolysis...
Despite similarities in their enzymic properties, diphtheria toxin (DT) and exotoxin A (ETA) of Pseudomonas aeruginosa have major differences structure action: consequently, the question possible evolutionary relatedness these two proteins remains unanswered. Here we report existence significant amino acid sequence homology between domain DT that ETA. Major segments may be aligned with high percentages identity conservative substitutions. The homologous stretches ETA form much active-site...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDimeric form of diphtheria toxin: purification and characterizationStephen F. Carroll, Joseph T. Barbieri, R. John CollierCite this: Biochemistry 1986, 25, 9, 2425–2430Publication Date (Print):May 1, 1986Publication History Published online1 May 2002Published inissue 1 1986https://pubs.acs.org/doi/10.1021/bi00357a019https://doi.org/10.1021/bi00357a019research-articleACS PublicationsRequest reuse permissionsArticle Views237Altmetric-Citations46LEARN...