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J M Levin

Publications and source records attributed to J M Levin.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1989

The cDNA-derived amino acid sequence of chick heat shock protein Mr 90,000 (HSP 90) reveals a "DNA like" structure: potential site of interaction with steroid receptors.

We report cDNA sequence, the complete derived aa sequence, and a predicted secondary structure of the chick hsp 90, a protein which has been found to form complexes with steroid hormone receptors. The modelling of the most negatively charged "region A" indicates that the alpha-helices of this portion of hsp 90 mimick DNA configuration. We propose that this region can, in absence of hormone, interact with and cap the positively charged DNA-binding domain of steroid receptors.

Amino Acid Sequence↗
PubMed1989

A highly charged sequence of chick hsp90: a good candidate for interaction with steroid receptors.

The sequence of the entire chick 90 kDa heat shock protein (hsp90), the non hormone binding component of the heterooligomeric form of steroid receptors, is reported. A comparison of the amino acid sequence of the chick hsp90 to that of the homologous hsp90 from yeast to man, reveals 64-96% identity respectively, and even with E. coli hsp90 an identity of 44% is observed. Analysis of the sequence and a secondary structure prediction of chick hsp90 suggest that two hydrophilic regions A and B, predicted in alpha-helix may play a role in the interaction of hsp90 with other proteins such as steroid hormone receptors. While there are regions of the sequences completely conserved in all hsps90, the most negatively charged hydrophilic region (A) is absent in the E. coli protein.

Algorithms↗
PubMed1988

Improvements in a secondary structure prediction method based on a search for local sequence homologies and its use as a model building tool.

This report describes an optimised version of a secondary structure prediction method based on local homologies, using a new data base. A 63% prediction accuracy, for three states, was obtained after elimination of the protein to be predicted and all proteins with a percentage identity greater than 22% from the data base. This corresponds to a 5% increase in accuracy on the original method (Levin et al. FEBS Lett. 205 (1986) 303-308). The flexibility of the method to the incorporation of information extraneous to the prediction was demonstrated by the prediction of the homologous proteins in the data base. Using the percentage identity with the protein to be predicted, to weight the relative importance of each protein, for all proteins with a percentage identity greater than 30%, the mean correct prediction per chain was 87%. As a result this algorithm can be used during the molecular modelling process, both to give an idea of the structural similarity between two proteins and as an aid in the determination of the best alignment. Incorporation of the result of a protein folding type assignment based on the global amino-acid composition increased the overall prediction to 66%.

Algorithms↗
PubMed1988

Secondary structure prediction: combination of three different methods.

A combination of three complementary secondary structure prediction methods is presented. The methods used are the GOR III method, the Homologue method and a new method, the bit pattern method, which is based on hydrophilic/hydrophobic residue patterns. For this purpose a hydropathy scale was developed and is presented here. The combination algorithm (Combine method) was designed to take the best results of each method and use their differences in order to improve the prediction. The combination yields 65.5% correctly predicted residues in three states: alpha-helix (H), beta-strand (E) and aperiodic structure (C) which is an improvement ranging from 2.5 to 6.5% compared with the individual methods when tested with a 67-polypeptide chain database. Seventy-five per cent of the regular secondary structure (H and E) runs are correctly located and beta-sheet runs are much better located by the Combine method in comparison to the other methods.

Predictive Value of Tests↗
PubMed1988

Ketoprofen versus indomethacin in patients with acute gouty arthritis: a multicenter, double blind comparative study.

Fifty-nine patients with acute gouty arthritis entered into a 7-day multicenter, double blind trial of ketoprofen versus indomethacin. Patients were randomly assigned to receive 100 mg of ketoprofen (n = 29 patients) or 50 mg of indomethacin (n = 30 patients) 3 times a day. More than 90% of the patients in each group reported pain relief within the 1st day of treatment. By Day 5, 7 patients in the ketoprofen group and 6 in the indomethacin group discontinued treatment because of complete or substantial pain relief. At the end of the study, most patients in both groups were rated as having marked improvement both by the investigators and by self-assessment. Three patients in each group withdrew prematurely because of drug related gastrointestinal disorders. Ketoprofen compared favorably for efficacy and safety with indomethacin in the treatment of gouty arthritis.

Administration, Oral↗
PubMed1986

An algorithm for secondary structure determination in proteins based on sequence similarity.

A secondary structure prediction algorithm is proposed on the hypothesis that short homologous sequences of amino acids have the same secondary structure tendencies. Comparisons are made with the secondary structure assignments of Kabsch and Sander from X-ray data [(1983) Biopolymers 22, 2577-2637] and an empirically determined similarity matrix which assigns a sequence similarity score between any two sequences of 7 residues in length. This similarity matrix differs in many respects from that of the Dayhoff substitution matrix [(1978) in: Atlas of Protein Sequence and Structure, (Dayhoff, M.O. ed). vol. 5. suppl. 3, pp. 353-358, National Biochemical Research Foundation, Washington, DC]. This homologue method had a prediction accuracy of 62.2% over 3 states for 61 proteins and 63.6% for a new set of 7 proteins not in the original data base.

Amino Acid Sequence↗
PubMed1981

Conformational changes induced by salt in complexes of histones and superhelical nuclear DNA.

When HeLa cells are lysed in solutions containing a non-ionic detergent and 0.75 M-NaCl, structures are released that retain many of the morphological features of nuclei. These nucleoids contain all the nuclear DNA, RNA and the 'core' histones, but few other proteins characteristic of chromatin. Their DNA is intact. The core histones dissociate on raising the salt concentration. We have probed the structure of nucleoid-histone complexes using the intercalating dye, ethidium, or the RNA polymerase of Escherichia coli. Both have a higher affinity for superhelical DNA than they do for relaxed DNA. The binding of ethidium is measured fluorometrically, and using this probe we find that the DNA of nucleoids containing all the core histones behaves as if it were supercoiled slightly positively. As the salt concentration is increased, free energy characteristic of negative supercoiling appears between 0.92 M and 0.95 M-NaCl. This transition, which is reversible in the presence of the arginine-rich histones, occurs without dissociation of these histones from the DNA and so must reflect a conformational change in the complex. In contrast to the results with ethidium, we find that RNA polymerase can detect the presence of some negative free energy of supercoiling in nucleoids containing the core histones. The transformations of the free energy that can assist the binding of ethidium and RNA polymerase are discussed.

Binding Sites↗
PubMed1981

Reconstruction of complexes of histone and superhelical nuclear DNA.

When HeLa cells are lysed in solutions containing a non-ionic detergent and 2 M-NaCl, structures are released that retain many of the morphological features of nuclei. These nucleoids contain all the nuclear RNA and DNA but few of the proteins characteristic of chromatin. Their DNA is supercoiled and so intact. Using a simple and rapid procedure we have reconstructed nucleohistone complexes from nucleoids and the 'core' histones without breaking the DNA. We have probed the integrity and structure of the reconstructed complexes using a non-destructive fluorometric approach, which provides a general method for detecting agents that bind to DNA and alter its supercoiling. The superhelical status of the DNA in the reconstructed complexes is indistinguishable from that found in control nucleoids containing core histones. Experiments with micrococcal nuclease confirm that the DNA in the reconstructed complexes is organized into nucleosome-like structures. These, however, are spaced 145 base-pairs apart and not 200 base-pairs apart as is found in native chromatin.

DNA, Superhelical↗
PubMed1980

The contralateral diseased but asymptomatic carotid artery: to operate or not? An update.

Bilaterally diseased carotid arteries were demonstrated in 147 patients in a personal series of 535 carotid reconstructions. A general policy of operating only on symptomatic patients was followed. Although stenotic and ulcerated plaques were known to be present in the contralateral artery, they were not repaired unless new symptoms occurred. No strokes were observed in these patients in a 20 year follow-up period. Twelve percent of the patients became symptomatic, leading to new arteriograms and a second artery repair. The patients at risk and their families were carefully instructed to report any symptoms of cerebrovascular insufficiency. If meticulous follow-up is carried out, the prophylactic repair of a truly asymptomatic diseased carotid artery is not believed necessary to prevent stroke.

Arterial Occlusive Diseases↗
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↗