Wyniki wyszukiwania - Biblioteka Nauki

1

The effect of the Glu342Lys mutation in α1-antitrypsin on its structure, studied by molecular modelling methods.

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Jezierski G. , Pasenkiewicz-Gierula M.

Acta Biochimica Polonica

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2001

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tom 48

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nr 1

65-75

EN

The structure of native α1-antitrypsin, the most abundant protease inhibitor in human plasma, is characterised primarily by a reactive loop containing the centre of proteinase inhibition, and a β-sheet composed of five strands. Mobility of the reactive loop is confined as a result of electrostatic interactions between side chains of Glu342 and Lys290, both located at the junction of the reactive loop and the β structure. The most common mutation in the protein, resulting in its inactivation, is Glu342→Lys, named the Z mutation. The main goal of this work was to investigate the influence of the Z mutation on the structure of α1-antitrypsin. Commonly used molecular modelling methods have been applied in a comparative study of two protein models: the wild type and the Z mutant. The results indicate that the Z mutation introduces local instabilities in the region of the reactive loop. Moreover, even parts of the protein located far apart from the mutation region are affected. The Z mutation causes a relative change in the total energy of about 3%. Relatively small root mean square differences between the optimised structures of the wild type and the Z mutant, together with detailed analysis of 'conformational searching' process, lead to the hypothesis that the Z mutation principally induces a change in the dynamics of α1-antitrypsin.

2

The identification and the elimination of clashes in the structure of an early-stage intermediate in the protein folding process

100%

Baster Z.

Bio-Algorithms and Med-Systems

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2013

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tom Vol. 9, no. 4

199--207

EN

The model (under consideration) to simulate the protein folding process assumes two steps: early stage (ES) and late stage (LS). The first is assumed to define the preliminary structure, which when applied to an optimization procedure, may produce the proper structure of the protein. However, the ES model produces the structures with clashes. This work demonstrates the possible solution to remove clashes before proceeding to the LS. Additionally, the presented solution describes mathematically the precession phenomenon, which might be useful in other fields of studies aside from protein folding such as medical imaging, quantum physics, and astronomy.

3

The variability of protein structure with respect to the hydrophobic core

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Banach M. , Wiśniowski Z. , Kalinowska B. , Konieczny L. , Roterman I.

Bio-Algorithms and Med-Systems

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2017

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tom Vol. 13, no. 2

63--67

EN

The application of the fuzzy oil drop model to the analysis of protein structure is shown using two proteins. The selection of these two examples is due to their opposite character. Two proteins were selected representing very high order and very high disorder with respect to the organized uni-central hydrophobic core in proteins (one centrally localized concentration of high hydrophobicity). These two cases are to show examples of the large spectrum of variability of local organization of the hydrophobic core in proteins. The importance of the observation presented in this paper is significant with respect to large sets of proteins discussed in separate publications.

4

Stability of two natural homologous proteins with different folds

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Konieczny L. , Banach M. , Roterman I.

Bio-Algorithms and Med-Systems

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2012

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tom Vol. 8, no. 2

185--193

EN

The applicability of the model for protein folding process simulation is presented using as the test two homologous proteins of different fold: helical in 3BD1 and β-structural form in 2PIJ [L. van Dorn, T. Newlove, S. Chang, W. Ingram, M. Cordes. Biochemistry 45, 10542 (2006)]. The folding process is assumed to be directed by hydrophobic core directing the hydrophobic residues toward the center of the molecule and exposing the hydrophilic residues on the surface. The “fuzzy oil drop” model is expressed by the 3-dimensional Gauss function which mimics the external force field. The value of Gauss function is interpreted as the hydrophobicity density calculated in any point of the space of the protein body. The accordance of idealized and observed hydrophobicity distributions (calculated according to Levitt function) measured using the Kullback-Leibler divergence entropy reveals good accordance in two homological proteins of different folds. The structural differences appeared to be easily explainable on the basis of “fuzzy oil drop” model.

5

Measurement of hydrophobicity distribution in proteins – complete redundant Protein Data Bank

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Sałapa K. , Kalinowska B. , Jadczyk T. , Roterman I.

Bio-Algorithms and Med-Systems

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2012

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tom Vol. 8, no. 2

195--206

EN

The divergence entropy: O/T and O/R measuring the distance between observed/theoretical and observed/random distributions was applied to identify the category of protein structures in respect to the hydrophobic core in protein molecules. The naive interpretation was applied treating the proteins of O/T < O/R as the molecules of hydrophobic core accordant with the theoretically assumed. The proteins of O/T > O/R are treated as representing the hydrophobic core not accordant with the assumed one. The large scale computing was performed (PDB data set) to reveal whether other than simple inequality relation should be used for this identification. The cluster analysis was applied to identify the relation O/T versus O/R as the discrimination factor to classify the category of proteins in respect to their structural form of hydrophobic core.

6

Ab initio protein structure prediction – the hydrophobicity distribution analysis

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Evangelista G. , Minervini G. , Polticelli F. , Malawski M. , Szepieniec T. , Flis Ł. , Prymula K. , Kochańczyk M. , Matczyńska E. , Wiśniowski Z. , Salapa K. , Banach M. , Roterman I.

Bio-Algorithms and Med-Systems

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2011

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tom Vol. 7, no. 2

5--12

EN

The three-dimensional structures generated for 20 “never born proteins” (NBP – random amino acid sequence with no significant homology to existing proteins) using two different techniques: ROSETTA (called R in the paper) and “fuzzy oil drop” model (called S in the paper) were compared to estimate the accordance with the assumed model estimating the influence of an external force field on the final structure of the protein. Selected structures are those corresponding to the highest (10 proteins) and lowest (10 proteins) RMS-D values obtained measuring the similarity between the R and S structures. The R structures generated according to an internal force field (the individual inter-molecular interaction) including solvation effects were analyzed using the “fuzzy oil drop” model as target model. The second applied model “fuzzy oil drop” generated structures characterized by an ordered hydrophobic core structure. 13 of the 20 selected S structures appeared to be accordant with the “fuzzy oil drop” model while 6 out of the 20 structures appeared to be accordant with external force field for R structures which suggests a general interpretation of the influence of an external force field on the folding simulation.

7

Investigation of the applicability range of protein threading software

100%

Jaworski S. , Sikorska C.

Current Topics in Biophysics. Supplement

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2011

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tom 34

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nr A: Posters

8

Dissimilar sequence: similar structure of proteins

100%

Banach M. , Konieczny L. , Roterman I.

Bio-Algorithms and Med-Systems

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2016

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tom Vol. 12, no. 3

117--121

EN

Sequence-to-structure relation is one of the major objects of the analysis of protein folding problem. The pair of two small proteins (domains) of similar structure (β-hairpin/α-helix/β-hairpin) generated by the chains of similar length (about 60 amino acids) with very low sequence similarity (15%) is the object of the comparable analysis of 3D structure. The criterion for similarity estimation is the status of polypeptide chain with respect to the hydrophobic core structure. The fuzzy oil drop model is applied to reveal the differentiated status of fragments of the well-defined secondary structure. This analysis allows the interpretation of the structure in other than the geometric form as it is made based on secondary structure classification. The two compared highly similar proteins appear to be different with respect to the hydrophobic core structure.

9

Scalar couplings in structure determination of proteins

100%

Ejchart A.

Bulletin of the Polish Academy of Sciences. Chemistry

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1999

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tom Vol. 47, No. 1

1-19

EN

Derivation of scalar couplings and their applications as structural constraints used in the determination of high resolution protein structures from nuclear magnetic resonance data is discussed.

10

Attaching a spin to a protein - site-directed spin labeling in structural biology

100%

Czogalla A. , Pieciul A. , Jezierski A. , Sikorski A. F.

Acta Biochimica Polonica

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2007

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tom 54

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nr 2

235-244

EN

Site-directed spin labeling and electron paramagnetic resonance spectroscopy have recently experienced an outburst of multiple applications in protein science. Numerous interesting strategies have been introduced for determining the structure of proteins and its conformational changes at the level of the backbone fold. Moreover, considerable technical development in the field makes the technique an attractive approach for the study of structure and dynamics of membrane proteins and large biological complexes at physiological conditions. This review focuses on a brief description of site-directed spin labeling-derived techniques in the context of their recent applications.

11

Application of divergence entropy to characterize the structure of lipid-binding proteins

100%

Rosicka R. , Banach M. , Roterman-Konieczna I.

Bio-Algorithms and Med-Systems

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2015

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tom Vol. 11, no. 3

171--176

EN

The lipid-binding protein present in the human brain is the object of this analysis. The expression of these proteins is especially important for nervous cell differentiation and their migration in the process of the development of the brain. The “fuzzy oil drop” model applied to the analysis of these proteins may suggest the mechanism of complex generation. It is shown that this type of complex may appear spontaneously in water environment. The presence of ligand does not imply any form of adaptation of the polypeptide chain to the ligand molecule. It can be speculated that ligand binding is of a static character without the necessity for mutual structural fitting. The structures of polypeptide in the apo- and complexed forms do not differ in respect to hydrophobic core formation. Such an interpretation is different than that observed in other ligand-binding proteins where the binding cavity needs to be specially fitted to the specific ligand. It can also be concluded that the lipid-binding process is of low specificity in this case.

12

Comparative analysis of HSV-1 temperature mutants proteins and their reactivity

100%

Litwinska B. , Biesiadecka A. , Gut W. , Kantoch M.

Acta Microbiologica Polonica

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1996

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tom 45

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nr 2

13

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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tom 48

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nr 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.

14

Structural studies of algal lectins with anti-HIV activity

88%

Ziółkowska N. E. , Wlodawer A.

Acta Biochimica Polonica

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2006

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tom 53

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nr 4

617-626

EN

A number of antiviral lectins, small proteins that bind carbohydrates found on viral envelopes, are currently in pre-clinical trials as potential drugs for prevention of transmission of human immunodeficiency virus (HIV) and other enveloped viruses, such as the Ebola virus and the coronavirus responsible for severe acute respiratory syndrome (SARS). Lectins of algal origin whose antiviral properties make them candidate agents for prevention of viral transmission through topical applications include cyanovirin-N, Microcystis viridis lectin, scytovirin, and griffithsin. Although all these proteins exhibit significant antiviral activity, their structures are unrelated and their mode of binding of carbohydrates differs significantly. This review summarizes the current state of knowledge of the structures of algal lectins, their mode of binding of carbohydrates, and their potential medical applications.

15

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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tom 48

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nr 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.

16

Protein intrachain contact prediction with most interacting residues (MIR)

88%

Acuña R. , Lacroix Z. , Papandreou N. , Chomilier J.

Bio-Algorithms and Med-Systems

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2014

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tom Vol. 10, no. 4

227--242

EN

The transition state ensemble during the folding process of globular proteins occurs when a sufficient number of intrachain contacts are formed, mainly, but not exclusively, due to hydrophobic interactions. These contacts are related to the folding nucleus, and they contribute to the stability of the native structure, although they may disappear after the energetic barrier of transition states has been passed. A number of structure and sequence analyses, as well as protein engineering studies, have shown that the signature of the folding nucleus is surprisingly present in the native three-dimensional structure, in the form of closed loops, and also in the early folding events. These findings support the idea that the residues of the folding nucleus become buried in the very first folding events, therefore helping the formation of closed loops that act as anchor structures, speed up the process, and overcome the Levinthal paradox. We present here a review of an algorithm intended to simulate in a discrete space the early steps of the folding process. It is based on a Monte Carlo simulation where perturbations, or moves, are randomly applied to residues within a sequence. In contrast with many technically similar approaches, this model does not intend to fold the protein but to calculate the number of non-covalent neighbors of each residue, during the early steps of the folding process. Amino acids along the sequence are categorized as most interacting residues (MIRs) or least interacting residues. The MIR method can be applied under a variety of circumstances. In the cases tested thus far, MIR has successfully identified the exact residue whose mutation causes a switch in conformation. This follows with the idea that MIR identifies residues that are important in the folding process. Most MIR positions correspond to hydrophobic residues; correspondingly, MIRs have zero or very low accessible surface area. Alongside the review of the MIR method, we present a new postprocessing method called smoothed MIR (SMIR), which refines the original MIR method by exploiting the knowledge of residue hydrophobicity. We review known results and present new ones, focusing on the ability of MIR to predict structural changes, secondary structure, and the improved precision with the SMIR method.

17

Monte Carlo simulations of protein-like heteropolymers.

88%

Sikorski A. , Romiszowski P.

Acta Biochimica Polonica

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2001

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tom 48

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nr 1

77-81

EN

Properties of a simple model of polypeptide chains were studied by the means of the Monte Carlo method. The chains were built on the (310) hybrid lattice. The residues interacted with long-range potential. There were two kinds of residues: hydrophobic and hydrophilic forming a typical helical pattern -HHPPHPP-. Short range potential was used to prefer helical conformations of the chain. It was found that at low temperatures the model chain formes dense and partially ordered structures (non-unique). The presence of the local potential led to an increase of helicity. The effect of the interplay between the two potentials was studied. After the collapse of the chain further annealing caused rearrangement of helical structures. Dynamic properties of the chain at low temperature depended strongly on the local chain ordering.

18

Hydrophobic core structure of macromomycin – the apoprotein of the antitumor antibiotic auromomycin – fuzzy oil drop model applied

88%

Roterman-Konieczna I. , Banach M. , Konieczny L.

Bio-Algorithms and Med-Systems

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2015

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tom Vol. 11, no. 3

177--181

EN

The fuzzy oil drop model was applied to analyze the structure of macromomycin, the apoprotein of the antitumor antibiotic auromomycin, revealing the differentiation of β-structural fragments present in β-sandwich. The seven-stranded antiparallel β-barrel and two antiparallel β-sheet ribbons represent the highly ordered geometry of the structure. However, participation in hydrophobic core formation appears different. The structure of the complete domain represents the status of the irregular hydrophobic core; however, some β-structural fragments appear to represent the hydrophobicity density distribution accordant with the idealized distribution of hydrophobicity as expected using the fuzzy oil drop model. Four β-structural fragments generating one common layer appear to be unstable in respect to the general structure of the hydrophobic core. This area is expected to be more flexible than other parts of the molecule. The protein binds the ligand – chromophore, two 2-methyl-2,4-pentanediol – in a well- defined cleft. The presence of this cleft makes the general structure of the hydrophobic core irregular (as it may be interpreted using the fuzzy oil drop model). Two short loops generated by two SS bonds fit very well to the general distribution of hydrophobicity density as expected for the model. No information about the potential amyloidogenic character of this protein is given in the literature; however, the specificity of the hydrophobicity distribution profile is found to be highly similar to the one observed in transthyretin (Banach M, Konieczny L, Roterman I. The fuzzy oil drop model, based on hydrophobicity density distribution, generalizes the influence of water environment on protein structure and function. J Theor Biol 2014;359:6–17), suggesting a possible tendency to turn to the amyloid form. A detailed analysis of macromomycin will be given, and a comparable analysis with other proteins of β-sandwich or β-barrel will be presented.

19

Structural and enzymatic properties of the sedolisin family of serine-carboxyl peptidases.

88%

Wlodawer A. , Li M. , Gustchina A. , Oyama H. , Dunn B. M. , Kohei Oda3

Acta Biochimica Polonica

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2003

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tom 50

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nr 1

81-102

EN

Sedolisins (serine-carboxyl peptidases) are proteolytic enzymes whose fold resembles that of subtilisin; however, they are considerably larger, with the mature catalytic domains containing approximately 375 amino acids. The defining features of these enzymes are a unique catalytic triad, Ser-Glu-Asp, as well as the presence of an aspartic acid residue in the oxyanion hole. High-resolution crystal structures have now been solved for sedolisin from Pseudomonas sp. 101, as well as for kumamolisin from a thermophilic bacterium, Bacillus novo sp. MN-32. The availability of these crystal structures enabled us to model the structure of mammalian CLN2, an enzyme which, when mutated in humans, leads to a fatal neurodegenerative disease. This review compares the structural and enzymatic properties of this newly defined MEROPS family of peptidases, S53, and introduces their new nomenclature.

20

MOFOID - not only the protein modelling server

88%

Szczesny P. , Wieczorek G. , Zielenkiewicz P.

Acta Biochimica Polonica

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2005

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tom 52

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nr 1

EN

MOFOID is a new server developed mainly for automated modeling of protein structures by their homology to the structures deposited in the PDB database. Selection of a template and calculation of the alignment is performed with the Smith-Waterman or Needleman-Wunsch algorithms implemented in the EMBOSS package. The final model is built and optimised with programs from the JACKAL package. The wide spectrum of options in the web-based interface and the possibility of uploading user’s own alignment make MOFOID a suitable platform for testing new approaches in the alignment building. The server is available at https://valis.ibb.waw.pl/mofoid/.