Biomedical subjects
Publications and source records attributed to I Svendsen.
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The complete primary structures of toxin II-14 from the Mexican scorpion Centruroides noxius Hoffmann and toxin gamma from the Brazilian scorpion Tityus serrulatus Lutz and Mello have been determined. Cleavage of toxin gamma after Met-6 with CNBr produced the 55-residue peptide 7-61, which maintained the four disulphide bonds but was not toxic to mice at a dose 3 times the lethal dose of native toxin gamma. Pairwise comparison by metric analysis of segment 1-50 of toxin gamma and the corresponding segments from two other South American scorpion toxins, five North American scorpion toxins, nine North African scorpion toxins and one Central Asian scorpion toxin showed that the three Brazilian toxins are intermediate between the North American and North African toxins. This result is consistent with the hypothesis that the South American and African continents were joined by a land connection in the distant past.
The serine proteinase inhibitor from barley seeds, chymotrypsin inhibitor 2(CI-2), has been crystallized in a molecular complex with subtilisin Novo (EC 3.4.21.14). The crystal structure of this complex has been determined at 2.1-A resolution by the molecular replacement method and partially refined by restrained-parameter least-squares methods. The present crystallographic R factor (SigmaFo[unk] - [unk]Fc/Sigma[unk]Fo[unk]) is 0.193. CI-2 is a member of the potato inhibitor 1 family; it is a serine proteinase inhibitor lacking disulfide bonds. Comparison of the subtilisin molecule in this complex with the native subtilisin shows that the two molecules are very similar in structure. The inhibitor binds in a mode presumably resembling that of a true substrate, but it is not cleaved. This is in accord with the reported structures of other serine proteinase-inhibitor complexes. CI-2 consists of a four-stranded mixed parallel and antiparallel beta-sheet against which an alpha-helix packs to form a hydrophobic core. A wide loop crossover connection between parallel strands 2 and 3 of the beta-sheet contains the reactive-site bond. The conformation of the four residues to either side of the reactive-site bond is similar to that of the analogous residues in the third domain of the turkey ovomucoid inhibitor (Kazal family); the overall polypeptide chain fold of these inhibitors and the location of the reactive site in the respective chains are different.
Previous studies of the structure and regulation of the deo operon in Escherichia coli have localized an internal regulated promoter, called deoP3, in front of the two distal genes in the operon. We report here the nucleotide sequence of the distal portion of the deoA, the deoA-deoB intercistronic region and the first part of the deoB gene, and show that deoP3 overlaps the distal segment of the deoA gene. The location of the internal promoter and the transcriptional start site were determined by means of 1) sequence homology to the consensus promoter sequence of E. coli, 2) high resolution S1 nuclease mapping of in vivo transcripts and 3) in vivo regulation of beta-galactosidase from low as well as high copy number P31acZ protein fusion vectors.
The deoC-deoA intercistronic region from Escherichia coli has been characterized by DNA and protein sequencing. This region consists of 129 bp and includes a regulatory element, which has also been found in other operons containing large intercistronic regions. Our results suggest that the regulatory element functions as a transcriptional attenuator, and therefore it seems likely that the primary role of this element is to effect differential expression of operon genes. Furthermore, we have unambiguously shown that the initiation codon for the deoA gene is UUG.
Ultracentrifugation and gel-filtration studies showed that the folate-binding protein from cow's milk possessed a remarkable aggregation tendency at pH 7.4. Aggregation was enhanced in the presence of folate which suggested an interrelationship between the mechanisms of ligand binding and polymerization. The degree of polymerization increased with increasing concentrations of binding protein. Thus, while the monomer prevailed at 1 nM, a polymer composed of more thn 32 monomers was formed at 130 microM. Two characteristics of folate binding, i.e., Scatchard plots that were convex upward and a ligand affinity that was inversely proportional to the concentration of binding protein, could be interpreted in terms of ligand binding to a polymerizing system in which the polymerization equilibria affect the ligand affinity.
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The sequence of the deoC gene of Escherichia coli K12 and the amino acid sequence of the corresponding protein, deoxyriboaldolase, has been established. The protein consists of 259 amino acids with a molecular weight of 27 737. The purified enzyme may exist both as a monomer and as a dimer. On the basis of amino acid composition, molecular weight and catalytic properties, the enzymes from E. coli and Salmonella typhimurium seem to be almost similar. They belong to the class I aldolases, which form Schiff base intermediates. Using data for the S. typhimurium enzyme, the lysine residue involved in the active site in the E. coli enzyme was tentatively identified.
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Human peripheral-blood mononuclear cells, separated by Isopaque-Ficoll flotation and E-rosette formation, were tested by the fluorescein fluorescence polarization method of Cercek & Cercek (the SCM test). The response to stimulation with PHA or cancer tissue leads to a decreased polarization value TP). The responding cells were present in the T-cell fraction (E-rosette-forming cells), which contained less than 10% macrophages and less than 1% cells with surface-bound Ig. Control experiments with the non-T-cell fraction gave different response patterns. The response of T cells from apparently healthy donors and patients with and without cancer were compared. All of the group of 16 healthy persons had a polarization value (P) which decreased (mean +/- s.e. = 23% +/- 2) after PHA stimulation, compared with no or little decrease after stimulation with cancer tissue, giving cancer indices (P cancer/PPHA) of 1.15--1.56. In 13 patients with carcinoma of the colon, stimulation with PHA produced little decrease of polarization, while stimulation with colonic cancer tissue decreased the polarization in all cases (mean +/- s.e. = 25% +/- 2). The corresponding cancer indices were 0.61--0.86. Seven of 10 colonic-cancer patients tested against ovarian cancer tissue did not respond, whilst 3 patients in this group responded and had a cancer index less than 1.0. Three patients with non-malignant diseases had response patterns similar to those of healthy persons, except for the lack of PHA response in the patient with ulcerative colitis. This method seems to open up new possibilities for evaluation of cancer patients, although further studies including many more patients are needed before any conclusion can be drawn as to the validity of the test.
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