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C Sander

Publications and source records attributed to C Sander.

At least 91 records · Page 5Linked to original sources
PubMed1995

Novel protein families in archaean genomes.

In a quest for novel functions in archaea, all archaean hypothetical open reading frames (ORFs), as annotated in the Swiss-Prot protein sequence database, were used to search the latest databases for the identification of characterized homologues. Of the 95 hypothetical archaean ORFs, 25 were found to be homologous to another hypothetical archaean ORF, while 36 were homologous to non-archaean proteins, of which as many as 30 were homologous to a characterized protein family. Thus the level of sequence similarity in this set reaches 64%, while the level of function assignment is only 32%. Of the ORFs with predicted functions, 12 homologies are reported here for the first time and represent nine new functions and one gene duplication at an acetyl-coA synthetase locus. The novel functions include components of the transcriptional and translational apparatus, such as ribosomal proteins, modification enzymes and a translation initiation factor. In addition, new enzymes are identified in archaea, such as cobyric acid synthase, dCTP deaminase and the first archaean homologues of a new subclass of ATP binding proteins found in fungi. Finally, it is shown that the putative laminin receptor family of eukaryotes and an archaean homologue belong to the previously characterized ribosomal protein family S2 from eubacteria. From the present and previous work, the major implication is that archaea seem to have a mode of expression of genetic information rather similar to eukaryotes, while eubacteria may have proceeded into unique ways of transcription and translation. In addition, with the detection of proteins in various metabolic and genetic processes in archaea, we can further predict the presence of additional proteins involved in these processes.

Animal Population Groups↗
PubMed1995

Transmembrane helices predicted at 95% accuracy.

We describe a neural network system that predicts the locations of transmembrane helices in integral membrane proteins. By using evolutionary information as input to the network system, the method significantly improved on a previously published neural network prediction method that had been based on single sequence information. The input data were derived from multiple alignments for each position in a window of 13 adjacent residues: amino acid frequency, conservation weights, number of insertions and deletions, and position of the window with respect to the ends of the protein chain. Additional input was the amino acid composition and length of the whole protein. A rigorous cross-validation test on 69 proteins with experimentally determined locations of transmembrane segments yielded an overall two-state per-residue accuracy of 95%. About 94% of all segments were predicted correctly. When applied to known globular proteins as a negative control, the network system incorrectly predicted fewer than 5% of globular proteins as having transmembrane helices. The method was applied to all 269 open reading frames from the complete yeast VIII chromosome. For 59 of these, at least two transmembrane helices were predicted. Thus, the prediction is that about one-fourth of all proteins from yeast VIII contain one transmembrane helix, and some 20%, more than one.

Amino Acid Sequence↗
PubMed1995

New protein functions in yeast chromosome VIII.

The analysis of the 269 open reading frames of yeast chromosome VIII by computational methods has yielded 24 new significant sequence similarities to proteins of known function. The resulting predicted functions include three particularly interesting cases of translation-associated proteins: peptidyl-tRNA hydrolase, a ribosome recycling factor homologue, and a protein similar to cytochrome b translational activator CBS2. The methodological limits of the meaningful transfer of functional information between distant homologues are discussed.

Alcohol Oxidoreductases↗
PubMed1995

The cytidylyltransferase superfamily: identification of the nucleotide-binding site and fold prediction.

The crystal structure of glycerol-3-phosphate cytidylyltransferase from B. subtilis (TagD) is about to be solved. Here, we report a testable structure prediction based on the identification by sequence analysis of a superfamily of functionally diverse but structurally similar nucleotide-binding enzymes. We predict that TagD is a member of this family. The most conserved region in this superfamily resembles the ATP-binding HiGH motif of class I aminoacyl-tRNA synthetases. The predicted secondary structure of cytidylyltransferase and its homologues is compatible with the alpha/beta topography of the class I aminoacyl-tRNA synthetases. The hypothesis of similarity of fold is strengthened by sequence-structure alignment and 3D model building using the known structure of tyrosyl tRNA synthetase as template. The proposed 3D model of TagD is plausible both structurally, with a well packed hydrophobic core, and functionally, as the most conserved residues cluster around the putative nucleotide binding site. If correct, the model would imply a very ancient evolutionary link between class I tRNA synthetases and the novel cytidylyltransferase superfamily.

Amino Acid Sequence↗
PubMed1995

Progress of 1D protein structure prediction at last.

Accuracy of predicting protein secondary structure and solvent accessibility from sequence information has been improved significantly by using information contained in multiple sequence alignments as input to a neural network system. For the Asilomar meeting, predictions for 13 proteins were generated automatically using the publicly available prediction method PHD. The results confirm the estimate of 72% three-state prediction accuracy. The fairly accurate predictions of secondary structure segments made the tool useful as a starting point for modeling of higher dimensional aspects of protein structure.

Amino Acid Sequence↗
PubMed1995

The use of position-specific rotamers in model building by homology.

In this study we concentrate on replacing side chains as a subtask of model building by homology. Two problems arise. How to determine potential low energy rotamers? And how to avoid the combinatorial explosion that results from the combination of many residues for which multiple good rotamers are predicted? We attempt to solve these problems by choosing position-specific rather than generalized rotamers and by sorting the residues that have to be modelled as a function of their freedom in rotamer space. The practical advantages of our method are the quality of the models for cases of high backbone similarity, the small amount of human intervention needed, and the fact that the method automatically estimates the reliability with which each residue has been modeled. Other methods described in this issue are probably more suitable if large backbone rearrangements or loop insertions and deletions need to be modeled.

Bacterial Proteins↗
PubMed1995

Nucleotide sequence and analysis of the centromeric region of yeast chromosome IX.

We have determined the nucleotide sequence of a cosmid (pIX338) containing the centromere region of yeast (Saccharomyces cerevisiae) chromosome IX. The complete nucleotide sequence of 33.8 kb was obtained by using an efficient directed sequencing strategy in combination with automated DNA sequencing on the A.L.F. DNA sequencer. Sequence analysis revealed the presence of 17 open reading frames (ORFs), four of them previously known yeast genes (sly12, pan1, sts1 and prl1), a tRNA gene and the centromere motif. Exhaustive database searches detected sequence homologues of known function for as many as 14 of the 17 ORFs. These include a mammalian tyrosine kinase substrate; the Escherichia coli cell cycle protein MinD; the human inositol polyphosphate-5-phosphatase (gene OCRL) involved in Lowe's syndrome, a developmental disorder; and helicases, for which the new yeast member defines a distinct DEAD/H-box subfamily. A surprisingly large fraction of the ORFs (at least six out of 17) in the centromeric region are apparently involved in RNA or DNA binding.

Adenosine Triphosphatases↗
PubMed1995

A Drosophila hsp70 gene contains long, antiparallel, coupled open reading frames (LAC ORFs) conserved in homologous loci.

A clone isolated from a Drosophila auraria heat-shock cDNA library presents two long, antiparallel, coupled (LAC) open reading frames (ORFs). One strand ORF is 1,929 nucleotides long and exhibits great identity (87.5% at the nucleotide level and 94% at the amino acid level) with the hsp70 gene copies of D. melanogaster, while the second strand ORF, in antiparallel in-frame register arrangement, is 1,839 nucleotides long and exhibits 32% identity with a putative, recently identified, NAD(+)-dependent glutamate dehydrogenase (NAD(+)-GDH). The overlap of the two ORFs is 1,824 nucleotides long. Computational analysis shows that this LAC ORF arrangement is conserved in other hsp70 loci in a wide range of organisms, raising questions about possible evolutionary benefits of such a peculiar genomic organization.

Amino Acid Sequence↗
PubMed1995

[Trichoblastoma. A tumor with follicular differentiation].

The purpose of this article is to inform about neoplasms with follicular differentiation, particularly trichoblastoma. In 1970 Headington divided neoplasms of the hair germ (trichogenic tumours) into four groups: purely epithelial without inductive changes (trichoblastomas), mixed epithelial-mesenchymal with inductive changes (trichoblastic fibromas), mixed epithelial-mesenchymal with inductive changes and advanced hair follicle formations (trichogenic trichoblastomas), and predominantly mesenchymal with an abortive dermal hair papilla (trichogenic myxoma). Meanwhile a new classification of neoplasms with follicular differentiation has been presented, according to which every neoplasm with follicular differentiation, benign structure (symmetrical, circumscribed, with vertical growth), and predominance of follicular germinative cells is called a trichoblastoma. Whether this neoplasm is malignant and if so to what degree is under discussion. This classification is gaining in acceptance among histopathologists but has not been accepted in the field of clinical dermatology.

Basal Cell Carcinoma↗
PubMed1995

[Hamartoma of the sebaceous follicle. An immunohistologic analysis with cytokeratins].

A 62-year-old man presented with a nodule 2 cm in diameter on his left cheek, which he had had since childhood. Histological examination showed a circumscribed dermal nodule composed of sebaceous lobules attached to sebaceous ducts and to an infundibular cyst-like structure connected to the epidermis. The wall was lined with squamous epithelium with a stratum granulosum. This structure was reminiscent of a sebaceous follicle. In addition, a melanocytic naevus of the compound type was found. Immunohistological investigations of the tumour with various cytokeratins revealed a pattern of expression characteristic for the mature sebaceous follicle.

Biomarkers, Tumor↗
PubMed1995

A method to predict functional residues in proteins.

The biological activity of a protein typically depends on the presence of a small number of functional residues. Identifying these residues from the amino acid sequences alone would be useful. Classically, strictly conserved residues are predicted to be functional but often conservation patterns are more complicated. Here, we present a novel method that exploits such patterns for the prediction of functional residues. The method uses a simple but powerful representation of entire proteins, as well as sequence residues as vectors in a generalised 'sequence space'. Projection of these vectors onto a lower-dimensional space reveals groups of residues specific for particular subfamilies that are predicted to be directly involved in protein function. Based on the method we present testable predictions for sets of functional residues in SH2 domains and in the conserved box of cyclins.

Algorithms↗
PubMed1995

[Doppler ultrasound findings in hemodilution with hydroxyethyl starch in intrauterine fetal retardation].

The surveillance of IUGR is one of the main indications of Doppler ultrasound for use in obstetrics. The volume replacement with hydroxyethyl starch is an effective therapy against plasma volume contraction diagnosed by an increase of hematocrit above 38%, which is often combined with IUGR. 48 patients with those problems were treated with middle molecular hydroxyethyl starch for at least 10 days. Doppler ultrasound was used before, within and after therapy. 39 of 48 patients (81%) showed pathological Doppler results in at least one of the examined vessels (uterine artery, umbilical artery, fetal aorta and middle cerebral artery). There is a correlation between normalisation of Doppler results, decrease of hematocrit and increase of the fetal growth indicated by ultrasound or birth weight, respectively. This therapy seems to be useful if it starts between 28th and 34th week of pregnancy; if we find at most two vessels with pathological Doppler results; and if there is an improvement of the Doppler results within therapy. A poor effect is to be expected if therapy begins after 36 weeks of pregnancy, if no change in pathological Doppler results can be found, if fetal vessels show pathological Doppler results and if there is a "notching" in the uterine artery. The group of patients with intrauterine growth retardation can be specified by Doppler ultrasound, which may profit from volume replacement. Doppler examinations are helpful to fetal surveillance within this therapy.

Adult↗
PubMed1995

Exploring the Mycoplasma capricolum genome: a minimal cell reveals its physiology.

We report on the analysis of 214kb of the parasitic eubacterium Mycoplasma capricolum sequenced by genomic walking techniques. The 287 putative proteins detected to date represent about half of the estimated total number of 500 predicted for this organism. A large fraction of these (75%) can be assigned a likely function as a result of similarity searches. Several important features of the functional organization of this small genome are already apparent. Among these are (i) the expected relatively large number of enzymes involved in metabolic transport and activation, for efficient use of host cell nutrients; (ii) the presence of anabolic enzymes; (iii) the unexpected diversity of enzymes involved in DNA replication and repair; and (iv) a sizeable number of orthologues (82 so far) in Escherichia coli. This survey is beginning to provide a detailed view of how M. capricolum manages to maintain essential cellular processes with a genome much smaller than that of its bacterial relatives.

Amino Acid Sequence↗
PubMed1995

3-D lookup: fast protein structure database searches at 90% reliability.

There are far fewer classes of three-dimensional protein folds than sequence families but the problem of detecting three-dimensional similarities is NP-complete. We present a novel heuristic for identifying 3-D similarities between a query structure and the database of known protein structures. Many methods for structure alignment use a bottom-up approach, identifying first local matches and then solving a combinatorial problem in building up larger clusters of matching substructures. Here, the top-down approach is to start with the global comparison and select a rough superimposition using a fast 3-D lookup of secondary structure motifs. The superimposition is then extended to an alignment of C alpha atoms by an iterative dynamic programming step. An all-against-all comparison of 385 representative proteins (150,000 pair comparisons) took 1 day of computer time on a single R8000 processor. In other words, one query structure is scanned against the database in a matter of minutes. The method is rated at 90% reliability at capturing statistically significant similarities. It is useful as a rapid preprocessor to a comprehensive protein structure database search system.

Amino Acid Sequence↗
PubMed1994

Correlation between the structure and biochemical activities of FtsA, an essential cell division protein of the actin family.

Cell division protein FtsA, predicted to belong to the actin family, is present in different cell compartments depending on its phosphorylation state. The FtsA fraction isolated from the cytoplasm is phosphorylated and capable of binding ATP, while the membrane-bound form is unphosphorylated and does not bind ATP. A variant of the protein FtsA102, in which the nucleotide binding site was destroyed by mutagenesis of a highly conserved residue predicted to be needed for the binding, does not bind ATP. Another variant, FtsA104, cannot be phosphorylated because the predicted phosphorylatable residue has been replaced by a non-phosphorylatable one. This protein although unable to bind ATP in vitro, is able to rescue the reversible ftsA2, the irreversible ftsA3 and, almost with the same efficiency, the ftsA16 amber alleles. Consequently, phosphorylation and ATP binding may not be essential for the function of FtsA. Alternatively they may have a regulatory role on the action of FtsA in the septator.

Actins↗