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Biomedical subjects

István Simon

Publications and source records attributed to István Simon.

7 recordsLinked to original sources
PubMed2003

Servers for sequence-structure relationship analysis and prediction.

We describe several algorithms and public servers that were developed to analyze and predict various features of protein structures. These servers provide information about the covalent state of cysteine (CYSREDOX), as well as about residues involved in non-covalent cross links that play an important role in the structural stability of proteins (SCIDE and SCPRED). We also discuss methods and servers developed to identify helical transmembrane proteins from large databases and rough genomic data, including two of the most popular transmembrane prediction methods, DAS and HMMTOP. Several biologically interesting applications of these servers are also presented. The servers are available through http://www.enzim.hu/servers.html.

Algorithms↗
PubMed2003

PSORT-B: Improving protein subcellular localization prediction for Gram-negative bacteria.

Automated prediction of bacterial protein subcellular localization is an important tool for genome annotation and drug discovery. PSORT has been one of the most widely used computational methods for such bacterial protein analysis; however, it has not been updated since it was introduced in 1991. In addition, neither PSORT nor any of the other computational methods available make predictions for all five of the localization sites characteristic of Gram-negative bacteria. Here we present PSORT-B, an updated version of PSORT for Gram-negative bacteria, which is available as a web-based application at http://www.psort.org. PSORT-B examines a given protein sequence for amino acid composition, similarity to proteins of known localization, presence of a signal peptide, transmembrane alpha-helices and motifs corresponding to specific localizations. A probabilistic method integrates these analyses, returning a list of five possible localization sites with associated probability scores. PSORT-B, designed to favor high precision (specificity) over high recall (sensitivity), attained an overall precision of 97% and recall of 75% in 5-fold cross-validation tests, using a dataset we developed of 1443 proteins of experimentally known localization. This dataset, the largest of its kind, is freely available, along with the PSORT-B source code (under GNU General Public License).

Bacterial Proteins↗
PubMed2003

SCide: identification of stabilization centers in proteins.

SUMMARY: SCide is a program to identify stabilization centers from known protein structures. These are residues involved in cooperative long-range contacts, which can be formed between various regions of a single polypeptide chain, or they can belong to different peptides or polypeptides in a complex. The server takes a PDB file as an input, and the result is presented in graphical or text format. AVAILABILITY: SCide is available on the web at http://www.enzim.hu/scide. The source code can be obtained from the authors on request.

Amino Acid Sequence↗
PubMed2002

Role of base flipping in specific recognition of damaged DNA by repair enzymes.

DNA repair enzymes induce base flipping in the process of damage recognition. Endonuclease V initiates the repair of cis, syn thymine dimers (TD) produced in DNA by UV radiation. The enzyme is known to flip the base opposite the damage into a non-specific binding pocket inside the protein. Uracil DNA glycosylase removes a uracil base from G.U mismatches in DNA by initially flipping it into a highly specific pocket in the enzyme. The contribution of base flipping to specific recognition has been studied by molecular dynamics simulations on the closed and open states of undamaged and damaged models of DNA. Analysis of the distributions of bending and opening angles indicates that enhanced base flipping originates in increased flexibility of the damaged DNA and the lowering of the energy difference between the closed and open states. The increased flexibility of the damaged DNA gives rise to a DNA more susceptible to distortions induced by the enzyme, which lowers the barrier for base flipping. The free energy profile of the base-flipping process was constructed using a potential of mean force representation. The barrier for TD-containing DNA is 2.5 kcal mol(-1) lower than that in the undamaged DNA, while the barrier for uracil flipping is 11.6 kcal mol(-1) lower than the barrier for flipping a cytosine base in the undamaged DNA. The final barriers for base flipping are approximately 10 kcal mol(-1), making the rate of base flipping similar to the rate of linear scanning of proteins on DNA. These results suggest that damage recognition based on lowering the barrier for base flipping can provide a general mechanism for other DNA-repair enzymes.

Base Pair Mismatch↗
PubMed2002

The role of dimerization in prion replication.

The central theme in prion diseases is the conformational transition of a cellular protein from a physiologic to a pathologic (so-called scrapie) state. Currently, two alternative models exist for the mechanism of this autocatalytic process; in the template assistance model the prion is assumed to be a monomer of the scrapie conformer, whereas in the nucleated polymerization model it is thought to be an amyloid rod. A recent variation on the latter assumes disulfide reshuffling as the mechanism of polymerization. The existence of stable dimers, let alone their mechanistic role, is not taken into account in either of these models. In this paper we review evidence supporting that the dimerization of either the normal or the scrapie state, or both, has a decisive role in prion replication. The contribution of redox changes, i.e., the temporary opening and possible rearrangement of the intramolecular disulfide bridge is also considered. We present a model including these features largely ignored so far and show that it adheres satisfactorily to the observed phenomenology of prion replication.

Animals↗
PubMed2002

Protein stability indicates divergent evolution of PD-(D/E)XK type II restriction endonucleases.

Type II restriction endonucleases recognize 4-8 base-pair-long DNA sequences and catalyze their cleavage with remarkable specificity. Crystal structures of the PD-(DE)XK superfamily revealed a common alpha/beta core motif and similar active site. In contrast, these enzymes show little sequence similarity and use different strategies to interact with their substrate DNA. The intriguing question is whether this enzyme family could have evolved from a common origin. In our present work, protein structure stability elements were analyzed and compared in three parts of PD-(DE)XK type II restriction endonucleases: (1) core motif, (2) active-site residues, and (3) residues playing role in DNA recognition. High correlation was found between the active-site residues and those stabilization factors that contribute to preventing structural decay. DNA recognition sites were also observed to participate in stabilization centers. It indicates that recognition motifs and active sites in PD-(DE)XK type II restriction endonucleases should have been evolutionary more conserved than other parts of the structure. Based on this observation it is proposed that PD-(DE)XK type II restriction endonucleases have developed from a common ancestor with divergent evolution.

Amino Acid Motifs↗