Biomedical subjects

Thomas Dandekar

Publications and source records attributed to Thomas Dandekar.

7 recordsLinked to original sources

PubMed2003

A software tool-box for analysis of regulatory RNA elements.

We describe an integrated tool-box to identify regulatory RNA elements. The RNA analyzer collects general and specific information on any submitted RNA sequence or batch of sequences in FASTA format. It determines and rapidly scans the different regions of an RNA (including 5' UTR, CDS, 3' UTR in mRNA) and screens for specific RNA signals (in each of these regions, e.g. polyA-site, AU rich region etc. in 3' UTR). It runs a fast folding RNA routine to provide an overview of the RNA fold. Furthermore it analyzes structure content, fold energy and stem loops. In addition, consensus templates are used to determine whether there are any functional structures present for translational control (template: IRE), structured RNA (template: tRNA consensus) or catalytic RNA (template: trans-splicing RNA), giving indications as to how well the structures found match to these templates. The tool box has been implemented as a WWW server at http://wb2x01.biozentrum.uni-wuerzburg.de/.

Internet↗

PubMed2003

A method for classifying metabolites in topological pathway analyses based on minimization of pathway number.

Metabolic pathway analysis based on the concept of elementary flux mode is a valuable tool for reconstruction of bacterial metabolisms and in predicting optimal conversion yields in biotechnology. However, pathway analysis of large and highly entangled metabolic networks meets the problem of combinatorial explosion of possible routes across the networks. Here we propose a method for coping with this problem by suitably classifying metabolites as external or internal. External metabolites are considered to have buffered concentrations while internal metabolites have to fulfil a balance condition at steady state. For many substances such as nutrients and excreted products, there are biochemical reasons to classify them as external. In addition, other substances (especially at central branching points) can operationally be considered external in order to avoid combinatorial explosion. We suggest to find such a classification of metabolites that minimizes the number of elementary flux modes (pathways). This is motivated by the objectives of finding such a description of the system that reduces as much as possible the amount of necessary data and of removing the ambiguity and arbitrariness in the classification of metabolites in an automated, systematic way. For networks of moderate size, the solution to this combinatorial minimization problem can be found by exhaustive search. To tackle also larger systems, a stochastic optimization program based on the Metropolis algorithm was developed. Both methods are applied, for illustration, to several reaction schemes including a larger network representing glutathione metabolism.

Combinatorial Chemistry Techniques↗

PubMed2003

Metabolites: a helping hand for pathway evolution?

The evolution of enzymes and pathways is under debate. Recent studies show that recruitment of single enzymes from different pathways could be the driving force for pathway evolution. Other mechanisms of evolution, such as pathway duplication, enzyme specialization, de novo invention of pathways or retro-evolution of pathways, appear to be less abundant. Twenty percent of enzyme superfamilies are quite variable, not only in changing reaction chemistry or metabolite type but in changing both at the same time. These variable superfamilies account for nearly half of all known reactions. The most frequently occurring metabolites provide a helping hand for such changes because they can be accommodated by many enzyme superfamilies. Thus, a picture is emerging in which new pathways are evolving from central metabolites by preference, thereby keeping the overall topology of the metabolic network.

Animals↗

PubMed2003

Toward computer-based cleavage site prediction of cysteine endopeptidases.

Identification of relevant substrates is essential for elucidation of in vivo functions of peptidases. The recent availability of the complete genome sequences of many eukaryotic organisms holds the promise of identifying specific peptidase substrates by systematic proteome analyses in combination with computer-based screening of genome databases. Currently available proteomics and bioinformatics tools are not sufficient for reliable endopeptidase substrate predictions. To address these shortcomings the bioinformatics tool 'PEPS' (Prediction of Endopeptidase Substrates) has been developed and is presented here. PEPS uses individual rule-based endopeptidase cleavage site scoring matrices (CSSM). The efficiency of PEPS in predicting putative caspase 3, cathepsin B and cathepsin L cleavage sites is demonstrated in comparison to established algorithms. Mortalin, a member of the heat shock protein family HSP70, was identified by PEPS as a putative cathepsin L substrate. Comparative proteome analyses of cathepsin L-deficient and wild-type mouse fibroblasts showed that mortalin is enriched in the absence of cathepsin L. These results indicate that CSSM/PEPS can correctly predict relevant peptidase substrates.

Animals↗

PubMed2002

Suspected utility of enzymes with multiple activities in the small genome Mycoplasma species: the replacement of the missing "household" nucleoside diphosphate kinase gene and activity by glycolytic kinases.

The small genome Mollicutes whose DNAs are completely sequenced (Mycoplasma genitalium, Mycoplasma pneumoniae, Mycoplasma pulmonis, and Ureaplasma urealyticum [parvum]) lack a gene (ndk) for the presumably essential nucleoside diphosphate kinase (NDPK). We hypothesized that other activities might replace NDPK activity. We found in M. genitalium G37(T), Mycoplasma pneumoniae FH(T), Mycoplasma fermentans PG18(T), and Mycoplasma capricolum subsp. capricolum Kid(T) that their 6-phosphofructokinases (6-PFKs), phosphoglycerate kinases (PGKs), pyruvate kinases (PKs), and acetate kinases (AKs), besides reactant ADP/ATP, could use other ribo- and deoxyribo-purine and pyrimidine NDPs and NTPs. These activities could compensate for the absence of an orthologous ndk gene in the Mycoplasmataceae. They suggest a metabolically varied and consequential role for unrelated and perhaps unsuspected "replacement" or compensatory enzymes that may confound metabolic prediction. We partially purified and biochemically characterized the PKs, 6-PFKs, PGKs, and AKs from M. capricolum subsp. capricolum Kid(T) and M. fermentans PG18(T).

Acetate Kinase↗

PubMed2002

Comparative genome analysis and pathway reconstruction.

Pathway reconstruction builds on genome and biochemical data with the aim of reconstructing higher level interactions between identified enzymes in a specific genome, in particular the different enzyme pathways (species or individual/patient). Metabolite flow in a pathway is analyzed by different tools, such as elementary mode analysis. This reveals key enzymes and pharmacological targets in the enzyme network. An overview of bioinformatic tools and algorithms for these tasks, application examples and recent results from these techniques are presented. Target selection, drug development and optimization can all be sped up using these approaches.

Animals↗

PubMedDate not supplied

A versatile structural domain analysis server using profile weight matrices.

The WEB tool "AnDom" assigns to a given protein sequence all experimentally determined structural domains contained within it, including multidomain and large proteins. The server uses profile specific matrices from custom generated multiple sequence alignments of all known SCOP domains (SCOP version 1.50). Prediction time is short allowing numerous applications for structural genomics including investigation of complex eucaryotic protein families. The WWW server is at http://www.bork.embl-heidelberg.de/AnDom, and profiles can be downloaded at ftp.bork.embl-heidelberg.de/pub/users/ schmidt/AnDom.

Amino Acid Sequence↗