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J M Levin

Publications and source records attributed to J M Levin.

10 recordsLinked to original sources
PubMed1991

Mutational and structural analysis of the nitrate reductase heme domain of Nicotiana plumbaginifolia.

We have analyzed four Nicotiana plumbaginifolia null mutants presumably affected in the heme domain of nitrate reductase. The DNA sequence of this domain has been determined for each mutant and for the wild type. Two mutations were identified as single base changes leading to, respectively, the substitution of a histidine residue by an asparagine (mutant E56) and to the appearance of an ochre stop codon (mutant E64). Based on the amino acid sequence homology between the nitrate reductase heme domain and mammalian cytochrome b5, we have predicted the three-dimensional structure of this domain. This showed that the nitrate reductase heme domain is structurally very similar to cytochrome b5 and it also confirmed that the residue involved in E56 mutation is one of the two heme-binding histidines. The two other mutations (mutants A1 and K21) were found to be, respectively, -1 and +1 frameshift mutations resulting in the appearance of an opal stop codon. These sequence data confirmed previous genetic and biochemical hypotheses on nitrate reductase-deficient mutants. Northern blot analysis of these mutants indicated that mutant E56 overexpressed the nitrate reductase mRNA, whereas the nonsense mutations present in the other mutants led to reduced levels of nitrate reductase mRNA.

Amino Acid Sequence↗
PubMed1991

Towards understanding the glycoprotein hormone receptors.

Lutropin (LH), follitropin (FSH) and thyrotropin (TSH), as well as choriogonadotropin (CG, which binds to the LH receptor) constitute the glycoprotein hormone family. Their 3 receptors have been cloned during the last few months. They belong to the large group of G-protein coupled membrane proteins, with their specific N-terminal domain likely to bind the hormone and the characteristic 7 membrane-spanning segments in their C-terminal moiety. The present review discusses the main results of amino acid sequence analysis performed on the glycoprotein hormone receptors. The putative extracellular head exhibits less than 45% homology over the 3 receptors, while approximately 70% residue conservation is found in the transmembrane moiety. Here only, limited sequence homologies (approximately 20%) can be found with other G-protein coupled receptors. The secondary structure predictions performed on the 3 receptors revealed that the polypeptide sequence predicted as ordered (either alpha-helix or beta-strand) were repeated evenly throughout the extracellular head with a period of approximately 25 amino acids. This analysis helped to define the intervening loops between this ordered stretches as potential candidates for bearing at least part of the binding site of the hormones. Some of the perspectives opened by the cloning of the receptors are described, like the production of the extracellular head of the porcine LH receptor in baculovirus-infected insect cells, and the exploration of the LH receptor's mechanism of functioning as a dimer.

Amino Acid Sequence↗
PubMed1991

The protein structure code: what is its present status?

Current methods of prediction of protein conformation are reviewed and the algorithms on which they rely are presented. For non-homologous proteins and after cross-validation the reported methods exhibit a probability index, i.e. the per cent of correctly predicted residues per predicted residues, of 63-65% with a standard deviation of the order of 7% for three conformational states--helix, beta-strand and coil. This present limitation in the accuracy of predictions that use only the information of the local sequence can be related essentially to the effect of long-range interactions specific for each protein family. The methods based on sequence similarity can improve the accuracy of prediction by expressing explicitly the homology of the protein to be predicted with proteins in the database. In these circumstances the probability index can reach 87% with a standard deviation of 6.6%. This property can be used for modeling homologous proteins by aiding in amino acid sequence alignments. The prediction of the tertiary structure of a protein is still limited to the case of modeling a structure based on the known three-dimensional structure of a homologous protein.

Algorithms↗
PubMed1990

Erythromycin failure with subsequent Pasteurella multocida meningitis and septic arthritis in a cat-bite victim.

We report the case of a 75-year-old woman who developed Pasteurella multocida meningitis and septic arthritis while being treated for a cat-bite wound infection with erythromycin. Review of the literature revealed that erythromycin has poor in vitro activity against this bacterium and has been associated with serious clinical failures. We recommend that erythromycin not be prescribed for empiric therapy of established animal-bite infections. Suggestions for optimal empiric therapy of animal-bite infections and the differential diagnosis of severe cat-bite-associated sepsis are discussed.

Aged↗
PubMed1990

Secondary structure prediction and protein design.

For non-homologous proteins, and after cross-validation, the methods reviewed in this article exhibit a probability index (percentage of correctly predicted residues per predicted residues) of 59-65.5% according to the methods employed with a standard deviation of 7% for three conformational states: alpha-helix, beta-strand and coil. These present limitations in the accuracy of prediction are related both to the limited number of known structures and to the effect of long-range interactions. The methods based on sequence similarity can improve the accuracy of prediction by expressing the homology of the protein to be predicted explicitly with proteins in the database. Under these circumstances, the probability index can reach 87% with a standard deviation of 6.6%. This property was used for modelling homologous proteins by assisting in amino acid sequence alignments. Examples will be given for the alignment of serine proteinases.

Amino Acid Sequence↗
PubMed1978

The dissociation of nuclear proteins from superhelical DNA.

Structures retaining many of the morphological features of nuclei may be released by gently lysing human cells in solutions containing non-ionic detergents and high concentrations of salt. These nucleoids contain superhelical DNA. Using a double-labelling procedure we have compared, at different salt concentrations, the amounts and types of protein associated with human nucleoides containings superhelical or relaxed DNA. We find that the slightly lysine-rich histones (H2A and H2B) but not the arginine-rich histones (H3 and H4) dissociate more slowly from nucleoids containing superhelical DNA than from those containing relaxed DNA. A protein of apparent molecular weight of 22000 also binds more tightly to superhelical DNA. We conclude that this protein and the slightly lysine-rich histones transmute free energy of supercoiling into binding energy when they bind to superhelical DNA.

Arginine↗
PubMed1978

Decreased serum complement in the Gardner-Diamond syndrome: immunofluorescent findings and association with angioimmunoblastic lymphadenopathy.

Immunologic and immunofluorescent profiles of two patients with the Gardner-Diamond syndrome are described. During the time ecchymoses were present, both patients had decreased serum complement levels; when the lesions healed, the serum complement level returned to normal. One patient had associated angioimmunoblastic lymphadenopathy and subepidermal deposits of immunoglobulin IgM at the basement membrane of ecchymotic skin. The other patient had a normal immunofluorescent pattern. Both patients had increased B-cell counts. The association of immunologic and immunofluorescent findings in patients with the Gardner-Diamond syndrome is suggestive and deserves further study.

Adult↗
PubMed1976

Therapy of dimethylbenzanthracene-induced mammary carcinomas in the rat by selective inhibition of steroidogenesis.

The effects of cyanoketone, a specific inhibitor of steroidogenesis at the levels of 3beta-hydroxysteroid oxidoreductase-dealta54-3-ketosteroid isomerase, the combination of cyanoketone with corticosterone, and corticosterone alone on the growth of dimethylbenzanthracene-induced hormone-dependent breast cancers in rats were compared with that produced by ovariectomy. Cyanoketone produces about as many regresssions of these cancers as does ovariectomy. However, cyanoketone with corticosterone results in a significant regression of tumors in all animals tested. This therapy also causes regression of significantly more tumors that are large at the beginning of treatment than does ovariectomy. These findings suggest that this kind of reversible blockade of steroidogenesis may be useful as a diagnostic tool in assessing the hormone dependence of breast tumors and as a possible therapeutic approach in the treatment of such tumors.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1975

Acinic cell carcinoma: collective review, including bilateral cases.

Bilateral acinic cell carcinoma of the parotid gland is rare. On the basis of one case and a review of 486 parotid acinic carcinomas, unilateral as well as bilateral, total parotidectomy seems to be the treatment of choice for this low-grade malignant neoplasm that recurs commonly following inadequate excision. If involved by tumor, the facial nerve must be taken. Metastases are more likely to lung and bone than to regional nodes. For this reason, radical neck dissection is not routinely indicated.

Adolescent↗