Exotoxin A of Pseudomonas aeruginosa is a secreted bacterial toxin capable of translocating a catalytic domain into mammalian cells and inhibiting protein synthesis by the ADP-ribosylation of cellular elongation factor 2. The protein is a single polypeptide chain of 613 amino acids. The x-ray crystallographic structure of exotoxin A, determined to 3.0-A resolution, shows the following: an amino-terminal domain, composed primarily of antiparallel a8-structure and comprising approximately half of the molecule; a middle domain composed of a-helices; and a carboxyl-terminal domain comprising approximately one-third of the molecule. The carboxyl-terminal domain is the ADP-ribosyltransferase of the toxin. The other two domains are presumably involved in cell receptor binding and membrane translocation.Exotoxin A of Pseudomonas aeruginosa is one member of a family of secreted bacterial toxins that are capable of covalently modifying specific target proteins within mammalian cells (1). Included in this family are the exotoxins of Corynebacterium diphtheriae (diphtheria toxin) and Vibrio cholerae (cholera toxin), Escherichia coli heat-labile toxin (LT), and exotoxins of Shigella dysenteria (shiga toxin) and Bacillus anthracis (anthrax toxins) as well as exotoxin A (2). Despite their diversity in size, subunit composition, cell specificity, and enzymatic activity, these toxins appear to share a similar multistep mechanism in which (i) the toxin binds to a receptor on the membrane surface of a target cell; (ii) the catalytic domain of the toxin is translocated into, or at a minimum into contact with, the cell cytoplasm; (iii) the catalytic moiety is then able to modify its target substrate. The toxins thus must have a receptor binding activity, a membrane translocation mechanism, and an enzymatic domain. It is characteristic that the receptor binding function and the enzymatic activity reside in separate structural components of the molecules, in separate subunits of an oligomer (cholera toxin, LT, shiga toxin) (3-5), in separate proteins (anthrax system) (6), or within a single monomeric polypeptide (diphtheria toxin, exotoxin A) (7,8).Several of the toxins (cholera toxin, LT, diphtheria toxin, and exotoxin A) catalyze transfer of the ADP-ribose moiety of oxidized nicotinamide adenine dinucleotide (NAD+) to target substrates (9-12). Diphtheria toxin and exotoxin A specifically ADP-ribosylate a modified histidine (diphthamide) of protein synthesis elongation factor 2, thereby inactivating the elongation factor and terminating peptide chain elongation in a target cell (13).Several intriguing mechanistic questions arise: (i) What are the mechanisms of membrane translocation by which the toxic factors enter the target cell cytoplasm? (ii) How is the membrane translocation and enzymic activation process controlled during intoxication? (iii) What is the mechanism of the ADP-ribosyltransferase reaction? Little structural information is available for members of this class of bacterial toxins. Crystals suitable for high re...

A synthetic approach to a two-dimensional grid polymer is proposed and the execution of initial steps is described. Pd-catalyzed coupling of (1,12-dicarba-closo-dodecaboran-1-yl)copper ( 10) with iodobenzene, mdiiodobenzene, and 1,3,5-triiodobenzene yielded the known 1,12-dicarba-closo-dodecaboran-1-ylbenzene (3) and the new m-bis(1,12-dicarba-closo-dodecaboran-1-yl)benzene (4) and 1,3,5-tris(1,12-dicarba-closo-dodecaboran-1yl)benzene (1), respectively. Each arm of the trigonal connector 1 was provided with one or two sticky tentacles by conversion to 1,3,5-tris [12-((3-(ethylthio)propyl)dimethylsilyl)-1,12-dicarba-closo-dodecaboran-1-yl]benzene (7) and 1,3,5-tris [12-(bis(3-(ethylthio)propyl)methylsilyl)-1,12-dicarba-closo-dodecaboran-1-yl]benzene (8). Linear coupling of carboranyl CH terminals through a mercury atom produced very stable dimeric structures from 3 and 4. The carborane 3, its mercury-linked dimer 13, the 1:1 complex of 13 with 2,2′-bipyridyl, and the 2:1 complex of 13 with 2,2′-bipyrimidyl have been structurally characterized by single-crystal X-ray crystallography, but crystals of 1 showed an intriguing disorder and could not be used for molecular structure determination. Grazing incidence IR spectra show that the tentacled species 7 and 8 adsorb firmly on the surface of gold, apparently without a strong preference for a particular orientation. At room temperature, the tritentacled species 7 can be removed readily and the hexatentacled species 8 more slowly by treatment with a THF solution containing fluoride, which severs the tentacles.

Square-planar palladium complexes containing tridentate ligands with PXP (X = C, N, O, S, and As) donor sets have been prepared. For [Pd(POP-R)(CH3CN)2l(BF4)2 complexes (where POP-R is bis((diethylphosphino)ethyl) ether, bis((diphenylphosphino)ethyl) ether, or bis((dicyclohexylphosphino)ethyl) ether), the POP-R ligands function as bidentate ligands.

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Pseudomonas aeruginosa exotoxin A is a representative of a class of enzymes, the mono-ADP-ribosyl transferases, which catalyze the covalent transfer of an ADP-ribose moiety of NAD+ to a target substrate. Availability of the three-dimensional structure of exotoxin A provides the opportunity for mapping substrate binding sites and suggesting which amino acid residues may be involved in catalysis. Data from several sources have been combined to develop a proposal for the NAD+ binding site of exotoxin A: the binding of NAD+ fragments adenosine, AMP, and ADP have been delineated crystallographically to 6.0, 6.0, and 2.7 A, respectively; significant sequence homology spanning 60 residues has been found between exotoxin A and diphtheria toxin, which has the identical enzymatic activity; iodination of exotoxin A, under conditions in which only tyrosine 481 is iodinated in the enzymatic domain, abolishes ADP-ribosyl transferase activity.