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1
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Prediction of the structure of the common perimitochondrial localization signal of nuclear transcripts in yeast

100%
Ejsmont R. K., Golik P., Stepien P. P.
Acta Biochimica Polonica
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2007
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vol. 54
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issue 1
55-61
EN
Many nuclear genes encoding mitochondrial proteins require specific localization of their mRNAs to the vicinity of mitochondria for proper expression. Studies in Saccharomyces cerevisiae have shown that the cis-acting signal responsible for subcellular localization of mRNAs is localized in the 3' UTR of the transcript. In this paper we present an in silico approach for prediction of a common perimitochondrial localization signal of nuclear transcripts encoding mitochondrial proteins. We computed a consensus structure for this signal by comparison of 3' UTR models for about 3000 yeast transcripts with known localization. Our studies show a short stem-loop structure which appears in most mRNAs localized to the vicinity of mitochondria. The degree of similarity of a given 3' UTR to our consensus structure strongly correlates with experimentally determined perimitochondrial localization of the mRNA, therefore we believe that the structure we predicted acts as a subcellular localization signal. Since our algorithm operates on structures, it seems to be more reliable than sequence-based algorithms. The good predictive value of our model is supported by statistical analysis.
2
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Peptidomics in veterinary science: focus on bovineparatuberculosis

100%
Piras C., Soggiu A., Greco V., Alloggio I., Bonizzi L., Roncada P.
Peptidomics
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2015
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vol. 2
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issue 1
EN
Bacterial infections represent a serious burden both for animal production and human health (zoonosis). Faster and more reliable diagnosis are mandatory in order to avoid economic losses and antibiotics misuse. The development of new potential diagnostic strategies for the immunodetection of pathogens is closely linked to the discovery of small polypeptides with immunogenic or immunoreactive activity. The candidate peptides used for this purpose must have several properties principally represented by their specificity and their location in the bacterial cell. Both proteomics, peptidomics and bioinformatics represent powerful complementary tools to discover specific immunoreactive peptides useful for diagnosis or vaccine. Peptidomics of Mycobacterium avium subsp. paratuberculosis (MAP) represents a good example of the potential of this discovery-phase. This review reports a comprehensive update of the current scientific knowledge about proteins and peptides of MAP with already documented humoral response. These findings, together with bioinformatics tools available, could be extremely useful to design a better strategy for subclinical bovine paratuberculosis diagnosis. The knowledge provided also represents a reliable example on the workflow to be followed in the direction of the diagnosis of other diseases through a peptidomic approach.
3
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Unexpected domain composition of MACC1 links MET signaling and apoptosis

100%
Kokoszyńska K., Kryński J., Rychlewski L., Wyrwicz L. S.
Acta Biochimica Polonica
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2009
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vol. 56
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issue 2
317-324
EN
Colorectal cancer, one of the most challenging malignancies, still has a limited number of recognized prognostic and predictive markers indicating appropriate treatment. MACC1 (metastasis-associated in colon cancer-1), a novel regulator of tumor growth and metastasis has recently been identified as an important prognostic factor of metastatic disease in colorectal cancer. The mechanism of MACC1 activity remains undetermined. Here we apply a combination of fold recognition and homology modeling algorithms to draft MACC1 function. The applied methods revealed that the MACC1 protein consists of four domains: ZU5, SH3, and two C-terminal death domains (DD). Previously a similar domain architecture (ZU5-DD) was observed in other proteins, involved mainly in signal transduction and apoptosis regulation. Based on the specific aspects of the closest homologues' biology functional hypotheses on MACC1 are proposed. A broad range of bioinformatic analyzes indicates that MACC1, besides its involvement in signal transduction from the MET receptor, links MET signaling and apoptosis.
4

Determining the structural amino acid attributes which are important in both protein thermostability and alkalophilicity: a case study on xylanase

100%
DELAVARI A., ZARE S., GHAEMI M. R., KASHFI R., EBRAHIMI M., TAHMASEBI A., EBRAHIMI M., EBRAHIMIE E.
BioTechnologia
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2014
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vol. 95
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issue 2
161-173
EN
Xylanases are used in the recycling of biomass and have other industrial applications including pulp bleaching. These enzymes are also applied in the baking industry and for the manufacture of animal feed. Such technologies as, for example, pulp bleaching entail high temperatures and high pHs. As a result, there is great demand from industry for thermostable and halostable forms of xylanase. Due to the relatively high variation in the thermo- and halo-stability of xylanases, feature selection was employed as a model to discover the important attributes of their amino acid sequences affecting the thermo- and halo-stability of the enzyme. A data set containing the amino acid sequences of xylanases with different thermo- and halostabilities was collected. Seventy-four amino acid attributes were obtained for each enzyme sequence. After running a feature selection algorithm for each of the thermo- and halostablity variables, features were classified as either important, unimportant or marginal. The results showed a significant correlation between structural amino acid attitudes and stability in harsh temperatures or alkaline conditions. Features such as lysine, glutamic acid, and positively/negatively charged residues showed a positive correlation with both the thermostability and alkalophilicity attributes of the protein. For the first time, we found attributes which were important for both stability at high temperatures as well as in alkaline conditions by mining sequence-derived amino acid attributes using data mining.
5
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Molecular cloning, expression and characterization of Bmserpin-2 gene from Bombyx mori

88%
Pan Y., Xia H., Lü P., Chen K., Yao Q., Chen H., Gao L., He Y., Wang L.
Acta Biochimica Polonica
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2009
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vol. 56
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issue 4
671-677
EN
Serpins are a broadly distributed family of protease inhibitors. In this study, the gene encoding Bombyx mori serpin-2 (Bmserpin-2) was cloned and expressed in E. coli. The Bmserpin-2 cDNA contains a 1125 bp open reading frame (ORF). The deduced protein has 374 amino-acid residues, contains a conserved SERPIN domain and shares extensive homology with other invertebrate serpins. RT-PCR analysis showed that Bmserpin-2 was expressed in all developmental stages of B. mori larvae and various larval tissues. Subcellular localization analysis indicated that Bmserpin-2 protein was located in the cytoplasm. Interestingly, real-time quantitative PCR revealed that the expression of Bmserpin-2 in the midgut of susceptible B. mori strain 306 significantly increased at 72 hours post inoculation (hpi) when infected with BmNPV. However, there was no significant increase of the Bmserpin-2 expression in resistant strain NB infected with BmNPV. Thus, our data indicates that Bmserpin-2 may be involved in B. mori antiviral response.
6
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Understanding the evolution of restriction-modification systems: Clues from sequence and structure comparisons.

88%
Bujnicki J. M.
Acta Biochimica Polonica
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2001
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vol. 48
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issue 4
935-967
EN
Restriction-modification (RM) systems comprise two opposing enzymatic activities: a restriction endonuclease, that targets specific DNA sequences and performs endonucleolytic cleavage, and a modification methyltransferase that renders these sequences resistant to cleavage. Studies on molecular genetics and biochemistry of RM systems have been carried out over the past four decades, laying foundations for modern molecular biology and providing important models for mechanisms of highly specific protein-DNA interactions. Although the number of known, relevant sequences 3D structures of RM proteins is growing steadily, we do not fully understand their functional diversities from an evolutionary perspective and we are not yet able to engineer new sequence specificities based on rational approaches. Recent findings on the evolution of RM systems and on their structures and mechanisms of action have led to a picture in which conserved modules with defined function are shared between different RM proteins and other enzymes involved in nucleic acid biochemistry. On the other hand, it has been realized that some of the modules have been replaced in the evolution by unrelated domains exerting similar function. The aim of this review is to give a survey on the recent progress in the field of structural phylogeny of RM enzymes with special emphasis on studies of sequence-structure-function relationships and emerging potential applications in biotechnology.
7
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Cloning of the Haemophilus influenzae Dam methyltransferase and analysis of its relationship to the Dam methyltransferase encoded by the HP1 phage.

88%
Bujnicki J. M., Radlińska M., Zaleski P., Piekarowicz A.
Acta Biochimica Polonica
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2001
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vol. 48
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issue 4
969-983
EN
In this paper we report cloning and experimental characterization of the DNA adenine methyltransferase (dam) gene from Haemophilus influenzae and comparison of ts product with the Dam protein from the lysogenic phage of H. influenzae, HP1. Molecular modeling of M.HinDam and M.HP1Dam was carried out, providing a framework for a comparative analysis of these enzymes and their close homologs in the tructural context. Both proteins share the common fold and essential cofactor-bind ng and catalytic residues despite overall divergence. However, subtle but significant differences in the cofactor-binding pocket have been identified. Moreover, while M.HinDam seems to contact its target DNA sequence using a number of loops, most of them are missing from M.HP1Dam. Analysis of both MTases suggests that their catalytic activity was derived from a common ancestor, but similar sequence specificities rose by convergence.
8
Content available remote

A common cis-element in promoters of protein synthesis and cell cycle genes

75%
Wyrwicz L. S., Gaj P., Hoffmann M., Rychlewski L., Ostrowski J.
Acta Biochimica Polonica
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2007
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vol. 54
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issue 1
89-98
EN
Gene promoters contain several classes of functional sequence elements (cis elements) recognized by protein agents, e.g. transcription factors and essential components of the transcription machinery. Here we describe a common DNA regulatory element (tandem TCTCGCGAGA motif) of human TATA-less promoters. A combination of bioinformatic and experimental methodology suggests that the element can be critical for expression of genes involved in enhanced protein synthesis and the G1/S transition in the cell cycle. The motif was identified in a substantial fraction of promoters of cell cycle genes, like cyclins (CCNC, CCNG1), as well as transcription regulators (TAF7, TAF13, KLF7, NCOA2), chromatin structure modulators (HDAC2, TAF6L), translation initiation factors (EIF5, EIF2S1, EIF4G2, EIF3S8, EIF4) and previously reported 18 ribosomal protein genes. Since the motif can define a subset of promoters with a distinct mechanism of activation involved in regulation of expression of about 5% of human genes, further investigation of this regulatory element is an emerging task.
9
Content available remote

Fold recognition insights into function of herpes ICP4 protein

75%
Wyrwicz L. S., Rychlewski L.
Acta Biochimica Polonica
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2007
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vol. 54
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issue 3
551-559
EN
ICP4 is an important factor regulating the life cycle of HSV1. This conserved protein has several molecular functions, including activation of expression of viral late gene transcripts and inhibition of immediate early genes. Although ICP4 and its Alphaherpesvirinae homologs (eg.: IE62 of VZV) have been subjects of various molecular studies, a complete view of their molecular function is lacking. Here we present the results of fold recognition and molecular modelling of ICP4 functional domains. The performed state-of-the-art bioinformatic fold recognition analysis identified a dual helix-turn-helix motif as a binding module of repressor activities (so called region 2 domain). The mapping of distant homology identified that a segment responsible for activation of late gene promoters (region 4) exhibits folding of uracil DNA glycosylase (UDG), but seems to be a non-functional homolog of UDG. Potential implications of the results are discussed.
10
Content available remote

Homologues of HSV-1 nuclear egress factor UL34 are potential phosphoinositide-binding proteins

75%
Wyrwicz L. S., Koczyk G., Rychlewski L.
Acta Biochimica Polonica
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2008
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vol. 55
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issue 1
207-213
EN
During the herpesvirus replication cycle, viral transcription, DNA replication, formation of capsids and DNA packaging occur in the nucleus. The subsequent nuclear egress of newly synthesized nucleocapsids is performed by budding of the inner leaflet of the nuclear membrane, which creates the primary envelope. Although products of two genes conserved throughout the Herpesviridae family (HSV-1 UL34 and UL31) have previously been shown to be involved in the execution of this process, the molecular basis of their activity is not clear. Here we present results of protein structure prediction for the conserved domain of UL34. The applied methodology suggests that this protein adopts a pleckstrin homology (PH) fold to perform its function. A detailed inspection of the ligand binding site strongly supports the hypothesis that UL34 orthologs can recognize phosphoinositides. Since previous works suggest that alterations of UL34 gene product result in a drastic impairment of primary envelopment of HSV-1 and trapping of capsids in the nucleus, the presented data may lead to the development of novel anti-herpetic therapeutic strategies where analogs of phosphoinositides are administered.
11
Content available remote

Cytomegalovirus immediate early gene UL37 encodes a novel MHC-like protein

75%
Wyrwicz L. S., Rychlewski L.
Acta Biochimica Polonica
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2008
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vol. 55
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issue 1
67-74
EN
The cytomegalovirus (CMV) genome encodes four clusters of genes expressed immediately after infection - i.e.: UL36-38, UL122-123, TRS1-IRS1, and US3. The general function of these genes is associated with inhibition of cellular mechanisms of antiviral response. Although several biological processes have been mapped onto specific gene products, the knowledge of the molecular mechanism of their activity remains fragmentary. Here, we report the application of protein structure prediction methods in assigning the function to a glycosylated domain encoded by UL37 of CMV (gpUL37, UL37x3). The discerned similarity clearly points out that this domain represents a novel type of a major histocompatibility complex (MHC)-like protein, and consequently may play a central role in an additional mechanism of escape from antiviral response.
12
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Content available

Electronegativity and intrinsic disorder of preeclampsia-related proteins

63%
Polanco C., Castañón-González J., Uversky V., Buhse T., Samaniego Mendoza J., Calva J.
Acta Biochimica Polonica
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2017
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vol. 64
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issue 1
99-111
EN
Preeclampsia, hemorrhage, and infection are the leading causes of maternal death in underdeveloped countries. Since several proteins associated with preeclampsia are known, we conducted a computational study which evaluated the commonness and potential functionality of intrinsic disorder of these proteins and also made an attempt to characterize their origin. The origin of the preeclampsia-related proteins was assessed with a supervised technique, a Polarity Index Method (PIM), which evaluates the electronegativity of proteins based solely on their sequence. The commonness of intrinsic disorder was evaluated using several disorder predictors from the PONDR family, the charge-hydropathy plot (CH-plot) and cumulative distribution function (CDF) analyses, and using the MobiDB web-based tool, whereas potential functionality of intrinsic disorder was studied with the D2P2 resource and ANCHOR predictor of disorder-based binding sites, and the STRING tool was used to build the interactivity networks of the preeclampsia-related proteins. Peculiarities of the PIM-derived polar profile of the group of preeclampsia-related proteins were then compared with profiles of a group of lipoproteins, antimicrobial peptides, angiogenesis-related proteins, and the intrinsically disordered proteins. Our results showed a high graphical correlation between preeclampsia proteins, lipoproteins, and the angiogenesis proteins. We also showed that many preeclampsia-related proteins contain numerous functional disordered regions. Therefore, these bioinformatics results led us to assume that the preeclampsia proteins are highly associated with the lipoproteins group, and that some preeclampsia-related proteins contain significant amounts of functional disorders.
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