Biomedical subjects
Publications and source records attributed to W Bode.
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The X-ray crystal structure of the complex formed by bovine beta-trypsin and the potent small inhibitor p-amidinophenylpyruvate at pH 7.6, has been determined by difference Fourier methods at 1.4 A resolution and subsequently refined to a crystallographic R value of 0.191, applying diagonal matrix least-squares procedures including energy constraints. The amidino and the phenyl group of this inhibitor are bound to the specificity pocket, essentially as previously observed in benzamidine-trypsin. The reactive Ser195 O gamma of trypsin forms a covalent bond of length 1.7 A to the carbonyl carbon of the pyruvate group. The hybridization of this carbonyl carbon is just between trigonal and tetrahedral. The imidazole ring of His57 is in a correct orientation to form bonds via its N epsilon 2 hydrogen to one of the carboxylate oxygens of p-amidinophenylpyruvate and to Ser195 O gamma. The probable proton shift makes Ser195 O gamma more nucleophilic and the attacked carbonyl carbon of p-amidinophenylpyruvate more electrophilic and thus facilitates bond formation. These specific interactions offer a qualitative explanation for the unique binding properties of p-amidinophenylpyruvate and for the applicability of the quantitative structure-activity relations previously found by Markwardt and coworkers for three series of p-amidinophenylalkanone compounds with carbonyl groups in alpha-, beta- and gamma-position to the phenyl ring.
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Aggregates of human and bovine fibrinogen were obtained under various conditions, ranging from segment-like precipitates to highly ordered paracrystals and crystals. Their biochemical characterization and the interpretation of their banding pattern by electron optical means was attempted. The observed extra vivum aggregation of fibrinogen without thrombin action, i.e. without cleavage of fibrino-peptides A and B is of particular interest with regard to Copley's theory of the endoendothelial fibrin lining. The in vivo formation of such fibrinogen gels is discussed.
Aggregates of human and bovine fibrinogen were obtained under various conditions, ranging from segment-like precipitates to highly ordered paracrystals and crystals. Their biochemical characterization and the interpretation of their banding pattern by electron optical means was attempted. The observed extra vivum aggregation of fibrinogen without thrombin action, i.e. without cleavage of fibrino-peptides A and B is of particular interest with regard to Copley's theory of the endoendothelial fibrin lining. The in vivo formation of such fibrinogen gels is discussed.
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Human alpha 1-proteinase inhibitor (alpha 1-PI) can form very stable complexes with chymotrypsinogen A or chymotrypsin if limited proteolysis by a contaminant proteinase is prevented with diisopropyl fluorophosphate. The contaminant proteinase cleaves the alpha 1-PI component in the alpha 1-PI-chymotrypsinogen A complex close to its N-terminus, between threonine-11 and aspartate-12 and the chymotrypsinogen A part between tyrosine-146 and threonine-147. By this modification the complex becomes unstable and dissociates into modified alpha 1-PI and neo-chymotrypsinogen A. A tritium labelling experiment shows that the contaminant proteinase is present in a 0.5-1.0% (w/w) ratio in the inhibitor preparation. These experiments indicate that alpha 1-PI is not a temporary inhibitor for these enzymes, as assumed by other authors. Isolated modified alpha 1-PI can be crystallized as tetragonal bipyramides from 2.6M sodium potassium phosphate pH 8.0. The crystals are suitable for three dimensional X-ray structure analysis. In spite of the cleavage of the susceptible peptide bond by chymotrypsinogen A, the C-terminal 3.6 kDa cleavage peptide remains tightly bound to the inhibitor by means of non-covalent interactions. In accordance with the result of the known complete amino-acid sequence of the inhibitor this finding offers an alternative explanation to the suggestion of alpha 1-PI being a double headed inhibitor. Isolated neo-chymotrypsinogen A can be activated to active chymotrypsin and can form a very labile 1 : 1 complex with alpha 1-PI, which dissociates rapidly into inactive inhibitor and neo-chymotrypsinogen.
The electron microscopic investigation of the renal medulla in calcium oxalate stone patients has shown the frequent occurrence of globoid microconcrements in the basal laminae of the collecting ducts and of the thin limbs in Henle's loop. They have a concentrically layered structure, the diameter is usually below 1.5 microns, rarely more than 3 microns. Some of these objects were also seen in the interstitial connective tissue. Tissue of stone-free patients exhibited either no or only few such microconcrements which were usually located in the interstitial space. Histochemical tests and energy dispersive microprobe analysis suggest that calcium phosphate and acid mucopolysaccharides are principal components of the microconcrements. There are indications that some microconcrements might be expelled from the basal laminae into the urinary space and may form agglomerations. They might then furnish nuclei for heterogeneous crystallization especially in cases without hypercalciuria or hyperoxaluria.
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Trypsin is a prototype of a large group of enzymes belonging to serine proteinases. The X-ray crystal-structure analyses of its proenzyme trypsinogen, of the active trypsin and of their complexes formed with the pancreatic trypsin inhibitor (PTI) have considerably enhanced our understanding of the mechanisms of activitation, action and inhibition. The trypsinogen is an incompletely folded molecule. Its substrate-binding site becomes only completely fixed upon the enzymatic cleavage of an N-terminal peptide. The contact regions of trypsin and PTI are almost complementary. The complex formed is a (stable) intermediate in the normal tryptic substrate-cleavage reaction.
The rate of endolysin synthesis in Salmonella typhimurium cells infected by bacteriophage P22 or L was taken as a measure for the activity of 23 gene product (the positive regulator for the "late" genes of P22 and L). Endolysin in coded for by gene 19. The amber mutations in gene 23 of P22 and L, used in this study, reduced the rate of endolysin synthesis by a factor of ca. 90 for P22 and of ca. 20 for L. In mixed infections with 19- and 23- mutants the 23 gene products of P22 and L ACT As positive regulators for the respective gene 19 in cis and in trans. Cross-specificity of the 23 gene products, i.e., turning on expression of gene 19 on a chromosome of the other species, could not be demonstrated.
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Two radiological methods were compared. More than 100 postmortem-coronary angiograms were taken with standard x-ray procedure and xeroradiography. Xeroradiography--with its "three dimensional view", edge enhancement and variability in exposure time--has certain advantages and appears to be useful in detection of pathological lesions and for documentation in postmortem coronary angiography.
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