By I. H. Madshus, H. Stenmark (auth.), Professor Dr. Dr. Klaus Aktories (eds.)
ADP-ribosylating pollution were the focal point of extensive learn for greater than 30 years. Researchers from different fields of technological know-how have taken an curiosity in those bacterial pollutants; they're studied, for instance, by means of microbiologists, biochemists, telephone biologists, and pharmacologists. There are relevant purposes for the large and nonetheless turning out to be curiosity in ADP ribosylating pollutants. First, insights into the constitution and features of the pollutants can be the most important to prevention and remedy of illnesses attributable to the toxin-producing infectious micro organisms. moment, the ADP-ribosylating pollution supply effective and infrequently detailed pharmacological instruments for the research of the physiological services in their aim proteins. The latter is mainly the case with cholera and pertussis pollution, which either alter the IX-subunits of heterotrimeric G-proteins inquisitive about sign transduction pathways. those pollution have proved beneficial in extending our uncomplicated figuring out of the legislation of hormone-controlled sign transduction. This quantity presents a evaluate and an replace of contemporary reports at the simple houses of bacterial ADP-ribosylating tbxins and/or exoenzymes. Our present wisdom of the cel lular access mechanisms of ADP-ribosylating pollution is reviewed by way of MADSHUS and STENMARK. WILSON and COLLIER then take care of contemporary insights into the enzyme mechanism and lively web site constitution of diphtheria toxin and Pseudomonas aeruginosa exotoxin A, which alter elongation issue 2. pollution which ADP-ribosylate heterotrimeric G-proteins concerned about trans membrane sign transduction are the topic of the subsequent chapters.
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Extra resources for ADP-Ribosylating Toxins
1977). EF-2 is a GTP-binding protein involved in protein biosynthesis by eukaryotic cells. ADP-ribosylated EF-2 is no longer able to mediate polypeptide chain elongation, and consequently, toxin-treated cells lose the ability to synthesize protein and ultimately die. Although the catalytic mechanism(s) of the modification reaction and the active sites of these Department of Microbiology and Molecular Genetics, Harvard Medical School and Shipley Institute of Medicine, 260 Longwood Avenue, Boston, MA 02115, USA Current TopIcs In Microbiology and Immunology.
35 5 Deletion of an Active-Site Loop Flanking the Catalytic Glutamic Acid 37 6 Future Prospects and Concluding Remarks. . . . . . . . . . . . . . . . . . 37 References ..................................................................... 38 1 Introduction Diphtheria toxin (DT), secreted by lysogenic strains of Corynebacterium diphtheriae carrying the phage-encoded DT gene, was the first ADP-ribosylating toxin for which the molecular mechanism of action was elucidated (COLLIER 1975; PAPPENHEIMER 1977), and for many years DT has served as an important model system for studying the pathogenesis of bacterial exotoxins (COLLIER 1982; JACOBSON and JACOBSON 1989; Moss and VAUGHAN 1990).
A Possible Rqle for an Active-Site Histidine in Catalysis. . . . . . . . . . . . . Effect of Carboxyl Side-Chain Position on Catalysis . . . . . . . . . . . . . . . Other Active-Site Residues ................................................... 1 4 Models for Binding of NAD to the Active Site. . . . . . . . . . . . . . . . . . 35 5 Deletion of an Active-Site Loop Flanking the Catalytic Glutamic Acid 37 6 Future Prospects and Concluding Remarks.
ADP-Ribosylating Toxins by I. H. Madshus, H. Stenmark (auth.), Professor Dr. Dr. Klaus Aktories (eds.)