Protein toxin

The conjugation of monoclonal antibodies (MoAbs) to radioisotopes, chemotherapeutic agents, and protein toxins has also been given consideration (65). Large amounts of human MoAbs can be produced by biotechnological means. 

Aeromonas hydrophila is a bacterium that causes diarrheal diseases and deep wound infections. These complications arise due to pore formation in sensitive cells by the protein toxin aerolysin. Proteolytic processing of the 52-kD precursor proaerolysin (Figure 10.34) produces the toxic form of the protein, aerolysin. Like a-hemolysin, aerolysin monomers associate to form a heptameric transmembrane pore. Michael Parker and coworkers have proposed... 

The bacterial culture converts a portion of the supplied nutrient into vegetative cells, spores, crystalline protein toxin, soluble toxins, exoenzymes, and metabolic excretion products by the time of complete sporulation of the population. Although synchronous growth is not necessary, nearly simultaneous sporulation of the entire population is desired in order to obtain a uniform product. Depending on the manner of recovery of active material for the product, it will contain the insolubles including bacterial spores, crystals, cellular debris, and residual medium ingredients plus any soluble materials which may be carried with the fluid constituents. Diluents, vehicles, stickers, and chemical protectants, as the individual formulation procedure may dictate, are then added to the harvested fermentation products. The materials are used experimentally and commercially as dusts, wettable powders, and sprayable liquid formulations. Thus, a... 

Protein toxins acting intracellularly are often composed of two subunits (A/B model). One subunit is catalytic (A-subunit) and the other is responsible for binding and cell entry (B-subunit). Following binding to an extracellular membrane receptor, the toxins are endocytosed. From the endosomes, the A-subunit is directly (pH dqDendent) transferred into the cytosol (e.g., diphtheria toxin and anthrax toxin) or the toxin is transported in a retrograde manner via the golgi to the ER (e.g., cholera toxin), where translocation into the cytosol occurs [1]. 

Protein toxins of this type are generally very potent and efficient because they act catalytically. The toxins usually activate or inactivate key eukaryotic proteins... 

Cholera toxin is a protein toxin of Vibrio choleme. Toxin ADP-ribosylates the a-subunit of the Gs heterotrimeric... 

Clostridial neurotoxins are bacterial protein toxins that consist of a heavy and a light chain connected by a disulfide bond and non-covalent interactions. They... 

A subfamily of Rho proteins, the Rnd family of small GTPases, are always GTP-bound and seem to be regulated by expression and localization rather than by nucleotide exchange and hydrolysis. Many Rho GTPase effectors have been identified, including protein and lipid kinases, phospholipase D and numerous adaptor proteins. One of the best characterized effector of RhoA is Rho kinase, which phosphorylates and inactivates myosin phosphatase thereby RhoA causes activation of actomyosin complexes. Rho proteins are preferred targets of bacterial protein toxins ( bacterial toxins). 

Numerous organisms, both marine and terrestrial, produce protein toxins. These are typically relatively small, and rich in disulfide crosslinks. Since they are often difficult to crystallize, relatively few structures from this class of proteins are known. In the past five years two dimensional NMR methods have developed to the point where they can be used to determine the solution structures of small proteins and nucleic acids. We have analyzed the structures of toxins II and III of RadiarUhus paumotensis using this approach. We find that the dominant structure is )9-sheet, with the strands connected by loops of irregular structure. Most of the residues which have been determined to be important for toxicity are contained in one of the loops. The general methods used for structure analysis will be described, and the structures of the toxins RpII and RpIII will be discussed and compared with homologous toxins from other anemone species. 

K Sandvig, S Olsnes. (1984). Receptor-mediated entry of protein toxins into cells. Acta Histochem 29 979-994. 

It is also important to have multiple biomarker masses to use in the search. In samples of protein toxins, and of many viruses (e.g., see Figure 12.2), only one of two proteins may be ionized and analyzed for database searching.15,74-76... 

Song X., Swanson B.I., Direct, ultrasensitive, and selective optical detection of protein toxins using multivalent interactions, Anal. Chem. 1999 71 2097-2107. 

Protein toxin possessing cytotoxic properties in vivo... 

Figure 21.2 Conceptualized construction of an A-B subunit protein toxin (left). The B chain contains a binding region for docking onto cell surfaces, while the A chain contains a catalytic site that produces cytotoxic affects intracellularly. The two subunits are joined by a disulfide bond that is reductively cleaved at the cellular level to allow the A subunit to affect cell death. A molecular model of ricin is on the right.

Protein toxins such as botulism, staphylococcal enterotoxin B, or ricin can be separated with gas or liquid chromatography, electrophoresis, or a combination. The pChemLab (Sandia National Laboratories Albuquerque, NM) series of instruments includes a hand-held Bio Detector. Proteins in the sample are labeled with fluorescent tags, and nanoliter volumes of samples are separated by microchannels etched into a glass chip. The separation occurs as the sample moves through the channels and identification is based on retention times. The analyses can be completed within 10 min. 

Davio, S.R., K.M. Kienle, and B.E. Collins. 1995. Interdomain interactions in the chimeric protein toxin sCD4(178)-PE40 a differential scanning calorimetry (DSC) study. Pharm Res 12 642-648. 

The following sections of this review will now transition into a unique group of protein toxins, the SEs and TSST-1. These proteins secreted by S. aureus vcovk in a different fashion versus the aforementioned binary toxins. In fact, these staphylococcal toxins do not enter a cell and do not directly injure the targeted cell surface. Toxin damage is insidiously indirect and caused by an over zealous response executed by the host s immune system. 

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