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P Bork

Publications and source records attributed to P Bork.

At least 163 records · Page 9Linked to original sources
PubMed1994

GeneQuiz: a workbench for sequence analysis.

We present the prototype of a software system, called GeneQuiz, for large-scale biological sequence analysis. The system was designed to meet the needs that arise in computational sequence analysis and our past experience with the analysis of 171 protein sequences of yeast chromosome III. We explain the cognitive challenges associated with this particular research activity and present our model of the sequence analysis process. The prototype system consists of two parts: (i) the database update and search system (driven by perl programs and rdb, a simple relational database engine also written in perl) and (ii) the visualization and browsing system (developed under C++/ET++). The principal design requirement for the first part was the complete automation of all repetitive actions: database updates, efficient sequence similarity searches and sampling of results in a uniform fashion. The user is then presented with "hit-lists" that summarize the results from heterogeneous database searches. The expert's primary task now simply becomes the further analysis of the candidate entries, where the problem is to extract adequate information about functional characteristics of the query protein rapidly. This second task is tremendously accelerated by a simple combination of the heterogeneous output into uniform relational tables and the provision of browsing mechanisms that give access to database records, sequence entries and alignment views. Indexing of molecular sequence databases provides fast retrieval of individual entries with the use of unique identifiers as well as browsing through databases using pre-existing cross-references. The presentation here covers an overview of the architecture of the system prototype and our experiences on its applicability in sequence analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

A hybrid protein kinase-RNase in an interferon-induced pathway?

The sequence of RNase L has been re-examined by computer analysis. We propose a molecular architecture of RNase L, with an unusual combination, in one protein chain, of 9 ankyrin-like repeats, a functional active protein kinase and a C-terminal catalytic RNase similar to the yeast protein, IRE1. The protein kinase may be involved in a new signal transduction pathway which remains to be discovered.

Amino Acid Sequence↗
PubMed1993

The modular architecture of a new family of growth regulators related to connective tissue growth factor.

Recently, several groups have characterized and sequenced members of a new family of growth regulators (originally called cef10, connective tissue growth factor, fisp-12, cyr61, or, alternatively, beta IG-M1 and beta IG-M2), all of which belong to immediate-early genes expressed after induction by growth factors or certain oncogenes. Sequence analysis of this family revealed the presence of four distinct modules. Each module has homologues in other extracellular mosaic proteins such as Von Willebrand factor, slit, thrombospondins, fibrillar collagens, IGF-binding proteins and mucins. Classification and analysis of these modules suggests the location of binding regions and, by analogy to better characterized modules in other proteins, sheds some light onto the structure of this new family.

Amino Acid Sequence↗
PubMed1993

The CUB domain. A widespread module in developmentally regulated proteins.

Sequence analysis has revealed the presence of 31 copies of an extracellular domain, here called CUB, in 16 functionally diverse proteins such as the dorso-ventral patterning protein tolloid, bone morphogenetic protein 1, a family of spermadhesins, complement subcomponents Cls/Clr and the neuronal recognition molecule A5. Most of them are known to be involved in developmental processes. Our analysis of this new family includes the identification of seven previously undescribed members, the characterization of conserved features and a topology prediction of this approximately 110 residue spanning domain, which suggests an antiparallel beta-barrel similar to those in immunoglobulins.

Amino Acid Sequence↗
PubMed1993

Prokaryotic members of a new family of putative helicases with similarity to transcription activator SNF2.

Cloning and sequence analysis of a new open reading frame from Bacillus cereus reveals the relationship to a recently identified family of putative eukaryotic transcription activators similar to the yeast SNF2 gene product. As a result of comparative analysis of sequence features conserved in all members of this family, a gene from a chilo iridescent virus, as well as a putative helicase from Escherichia coli (hepA), can also be grouped into this family. The unexpected presence of prokaryotic and viral sequences in the previously purely eukaryotic SNF2 family suggests a defined subgroup of DNA helicases present in all species, with specific function in transcription activation.

Adenosine Triphosphatases↗
PubMed1993

Convergent evolution of similar enzymatic function on different protein folds: the hexokinase, ribokinase, and galactokinase families of sugar kinases.

Kinases that catalyze phosphorylation of sugars, called here sugar kinases, can be divided into at least three distinct nonhomologous families. The first is the hexokinase family, which contains many prokaryotic and eukaryotic sugar kinases with diverse specificities, including a new member, rhamnokinase from Salmonella typhimurium. The three-dimensional structure of hexokinase is known and can be used to build models of functionally important regions of other kinases in this family. The second is the ribokinase family, of unknown three-dimensional structure, and comprises pro- and eukaryotic ribokinases, bacterial fructokinases, the minor 6-phosphofructokinase 2 from Escherichia coli, 6-phosphotagatokinase, 1-phosphofructokinase, and, possibly, inosine-guanosine kinase. The third family, also of unknown three-dimensional structure, contains several bacterial and yeast galactokinases and eukaryotic mevalonate and phosphomevalonate kinases and may have a substrate binding region in common with homoserine kinases. Each of the three families of sugar kinases appears to have a distinct three-dimensional fold, since conserved sequence patterns are strikingly different for the three families. Yet each catalyzes chemically equivalent reactions on similar or identical substrates. The enzymatic function of sugar phosphorylation appears to have evolved independently on the three distinct structural frameworks, by convergent evolution. In addition, evolutionary trees reveal that (1) fructokinase specificity has evolved independently in both the hexokinase and ribokinase families and (2) glucose specificity has evolved independently in different branches of the hexokinase family. These are examples of independent Darwinian adaptation of a structure to the same substrate at different evolutionary times. The flexible combination of active sites and three-dimensional folds observed in nature can be exploited by protein engineers in designing and optimizing enzymatic function.

Amino Acid Sequence↗
PubMed1993

Hundreds of ankyrin-like repeats in functionally diverse proteins: mobile modules that cross phyla horizontally?

Based on pattern searches and systematic database screening, almost 650 different ankyrin-like (ANK) repeats from nearly all phyla have been identified; more than 150 of them are reported here for the first time. Their presence in functionally diverse proteins such as enzymes, toxins, and transcription factors strongly suggests domain shuffling, but their occurrence in prokaryotes and yeast excludes exon shuffling. The spreading mechanism remains unknown, but in at least three cases horizontal gene transfer appears to be involved. ANK repeats occur in at least four consecutive copies. The terminal repeats are more variable in sequence. One feature of the internal repeats is a predicted central hydrophobic alpha-helix, which is likely to interact with other repeats. The functions of the ankyrin-like repeats are compatible with a role in protein-protein interactions.

Amino Acid Sequence↗
PubMed1993

Molecular modelling of the Norrie disease protein predicts a cystine knot growth factor tertiary structure.

The X-lined gene for Norrie disease, which is characterized by blindness, deafness and mental retardation has been cloned recently. This gene has been thought to code for a putative extracellular factor; its predicted amino acid sequence is homologous to the C-terminal domain of diverse extracellular proteins. Sequence pattern searches and three-dimensional modelling now suggest that the Norrie disease protein (NDP) has a tertiary structure similar to that of transforming growth factor beta (TGF beta). Our model identifies NDP as a member of an emerging family of growth factors containing a cystine knot motif, with direct implications for the physiological role of NDP. The model also sheds light on sequence related domains such as the C-terminal domain of mucins and of von Willebrand factor.

Amino Acid Sequence↗
PubMed1993

A fast, sensitive pattern-matching approach for protein sequences.

Pattern-matching algorithms are a powerful tool for finding similarities and relationships among the steadily growing amount of known protein sequences. We present a fast, sensitive pattern-matching algorithm that describes a pattern by its physico-chemical properties rather than by occurrence of amino acids, using a fast, dynamic programming algorithm. Selected examples will demonstrate applications and advantages of our approach.

Algorithms↗