SEARCH · PubMed Health

Results for “Models, Structural”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources

PubMedDate not supplied

An alternative structure model for the polypentapeptide in elastin.

Polypentapeptides (GVGVP)n which are designed in analogy to the connective tissue protein elastin are reported to transform various kinds of energy into mechanical work by the so-called deltaT(t)-mechanism in cross-linked macroscopic polypentapeptide (PPP) films. In the literature, the responsible element of conformation in such polypeptides is described as a beta-spiral and the deltaT(t) effect is explained as a sudden change of macroconformation of single polypeptide molecules from an extended but not regular state below a transition temperature T(t) to the beta-spiral above T(t). We examined the secondary structure of the linear PPP C(GVGVP)6 in solution with DSC, CD, UV absorption, FTIR and NMR spectroscopy. The results suggest that the beta-spiral is not present in the conformational structure of the PPP molecules. The antiparallel beta-sheet is proposed to be the basic regular part of conformation because it agrees with all spectroscopic data. As a consequence, the elasticity of natural elastin must be considered from a new perspective.

Amino Acid Sequence↗

PubMed1992

Forecasting health: data needs and implications for model structure.

An agenda for analysing data on the health and functioning of the elderly must indicate new types of data to be collected, innovations in data collection strategies and new methods for analysis and forecasting. The required research agenda is broad and will require inputs from investigators in a number of disciplines. The data and methods required will need to be developed in order to reflect national, regional and local variations in the health phenomena under study; they will also have to be responsive to these variations. In the end, however, if the investment is to be most useful, it must be integrated into simulation and forecasting models, the mechanics of which are based on individual-level processes and not on the elements of the service system.

Breast Neoplasms↗

PubMed1996

An RNA recognition motif in Wilms' tumour protein (WT1) revealed by structural modelling.

The Wilms' tumour suppressor gene 1 (WT1) (1,2) encodes four C2H2 zinc finger-containing proteins (3) critical for normal mammalian urogenital development (4). Mutations in this gene are observed in the childhood kidney cancer, Wilms' tumour (WT) (5). WT1 can bind specific DNA targets within the promoters of many genes (6-9) and both transcriptional repression and activation domains have been identified (10). On this basis, it has been assumed that regulation of transcription is the basis of WT1 tumour suppressor activity. However, subnuclear localization studies have revealed an association between WT1 proteins and 'speckled bodies' within the nucleus. Degradation of nuclear RNA in cells expressing WT1 abolishes this speckled localization and WT1 co-immunoprecipitates with a number of spliceosomal proteins, suggesting that it may also bind to RNA (11). Using structural rather than sequence comparison, we have now identified an evolutionarily conserved N-terminal RNA recognition motif (RRM) in all known WT1 isoforms similar to that in the constitutive splicing factor U1A. Given the association between WT1 mutations and Wilms' tumours, this study, together with other recent findings, may suggest a novel tumour suppression mechanism.

Amino Acid Sequence↗

PubMed2006

Self-modeling structure of evoked postsynaptic potentials.

With the simplicity of the synaptic structure and physiology at neuromuscular junctions (NMJs) of crayfish and the given transmitter being released in quantal packets, a detailed assessment in the fundamental processes of chemical synaptic transmission is possible. Since the quantal event is the basic element of transmission, we consider an approach to further understand the characteristics of quantal responses. In this study, we introduce a method for combining information across excitatory postsynaptic potentials (EPSPs) that are quantal in nature. The method is called self-modeling regression, known in the statistics literature as SEMOR. This method illustrates that the differing timing and heights of EPSPs can be described with four coefficients measuring affine (shift and scale) transformations of the x and y axes. We demonstrate that this relationship allows us to provide a unified schema for the many functionals currently used in the literature, such as peak amplitude, tau, latency, area under the curve, or decay time. Computer code in R is available on the internet to perform the analysis.

Animals↗

PubMed1997

Integrating database homology in a probabilistic gene structure model.

We present an improved stochastic model of genes in DNA, and describe a method for integrating database homology into the probabilistic framework. A generalized hidden Markov model (GHMM) describes the grammar of a legal parse of a DNA sequence. Probabilities are estimated for gene features by using dynamic programming to combine information from multiple sensors. We show how matches to homologous sequences from a database can be integrated into the probability estimation by interpreting the likelihood of a sequence in terms of the bit-cost to encode a sequence given a homology match. We also demonstrate how homology matches in protein databases can be exploited to help identify splice sites. Our experiments show significant improvements in the sensitivity and specificity of gene structure identification when these new features are added to our gene-finding system, Genie. Experimental results in tests using a standard set of annotated genes showed that Genie identified 95% of coding nucleotides correctly with a specificity of 91%, and 77% of exons were identified exactly.

Algorithms↗

PubMed2006

Binding of oxovanadium ions to the major and minor grooves of DNA duplex: stability and structural models.

Vanadate induces DNA strand breaks in cultured human fibroblasts at doses that are relative to the occupational exposure. Oxovanadium compounds also exert preventive effects against chemical carcinogenesis in animals and form complexes with DNA in vivo. This study was designed to examine the interaction of calf-thymus DNA with VO2+ and VO3 ions in aqueous solution at physiological pH, with a constant DNA concentration of 12.5 mmol/L and vanadium-DNA (phosphate) molar ratios (r) of 1:160 to 1:2. Capillary electrophoresis and Fourier transform infrared difference spectroscopy were used to determine the cation binding site, the binding constant, the helix stability, and DNA conformation in the oxovanadium-DNA complexes. Structural analysis showed that VO2+ binds DNA through guanine and adenine N-7 atoms and the backbone PO2 group with apparent binding constants of KG = 8.8 x 10(5) (mol/L)-1 and KA = 3.4 x 10(5) (mol/L)-1. The VO3 shows weaker binding through thymine, adenine, and guanine bases, with K = 1.9 x 10(4) (mol/L)-1 and no interaction with the backbone phosphate group. A partial B-to-A DNA transition occurred upon VO-DNA complexation, while DNA remains in the B-family structure in the VO3 complexes.

Animals↗

PubMed1998

A structural model of picornavirus leader proteinases based on papain and bleomycin hydrolase.

The leader (L) proteinases of aphthoviruses (foot-and-mouth disease viruses) and equine rhinovirus serotypes 1 and 2 cleave themselves from the growing polyprotein. This cleavage occurs intramolecularly between the C terminus of the L proteinases and the N terminus of the subsequent protein VP4. The foot-and-mouth disease virus enzyme has been shown, in addition, to cleave at least one cellular protein, the eukaryotic initiation factor 4G. Mechanistically, inhibitor studies and sequence analysis have been used to classify the L proteinases as papain-like cysteine proteinases. However, sequence identity within the L proteinases themselves is low (between 18% and 32%) and only 14% between the L proteinases and papain. Secondary structure predictions, sequence alignments that take into account the positions of the essential catalytic residues, and structural considerations have been used in this study to investigate more closely the relationships between the L proteinases and papain. In spite of the low sequence identities, the analyses strongly suggest that the L proteinases of foot-and-mouth disease virus and of equine rhinovirus 1 have a similar overall fold to that of papain. Regions in the L proteinases corresponding to all five alpha-helices and seven beta-sheets of papain could be identified. Further comparisons with the proteinase bleomycin hydrolase, which also displays a papain topology in spite of important differences in size and amino acid sequence, support these conclusions and suggest how a C-terminal extension, present in all three L proteinases, and predicted to be an alpha-helix, might enable C-terminal self-processing to occur.

Amino Acid Sequence↗

PubMed2005

UVA-visible photo-excitation of guanine radical cations produces sugar radicals in DNA and model structures.

This work presents evidence that photo-excitation of guanine radical cations results in high yields of deoxyribose sugar radicals in DNA, guanine deoxyribonucleosides and deoxyribonucleotides. In dsDNA at low temperatures, formation of C1'* is observed from photo-excitation of G*+ in the 310-480 nm range with no C1'* formation observed > or =520 nm. Illumination of guanine radical cations in 2'dG, 3'-dGMP and 5'-dGMP in aqueous LiCl glasses at 143 K is found to result in remarkably high yields (approximately 85-95%) of sugar radicals, namely C1'*, C3'* and C5'*. The amount of each of the sugar radicals formed varies dramatically with compound structure and temperature of illumination. Radical assignments were confirmed using selective deuteration at C5' or C3' in 2'-dG and at C8 in all the guanine nucleosides/tides. Studies of the effect of temperature, pH, and wavelength of excitation provide important information about the mechanism of formation of these sugar radicals. Time-dependent density functional theory calculations verify that specific excited states in G*+ show considerable hole delocalization into the sugar structure, in accord with our proposed mechanism of action, namely deprotonation from the sugar moiety of the excited molecular radical cation.

Cations↗

PubMed2004

Structural models of the bimetallic subunit at the A-cluster of acetyl coenzyme a synthase/CO dehydrogenase: binuclear sulfur-bridged Ni-Cu and Ni-Ni complexes and their reactions with CO.

The Ni(II)-dicarboxamido-dithiolato complexes (Et4N)2[Ni(NpPepS)] (1) and (Et4N)2[Ni(PhPepS)] (2) were used as Nid metallosynthons in the construction of higher nuclearity dinuclear Ni-Cu and Ni-Ni species to model the bimetallic Mp-Nid site of the A-cluster of acetyl coenzyme A synthase/CO dehydrogenase (ACS/CODH). Reaction of 1 with [Cu(neo)Cl] and [Ni(terpy)Cl2] in MeCN affords the dinuclear complexes (Et4N)[Cu(neo)Ni(NpPepS)] (3) and [Ni(terpy)Ni(NpPepS)] (4), respectively. Reaction of 2 with [Ni(dppe)Cl2] in MeCN yields [Ni(dppe)Ni(PhPepS)] (6). The Ni-Cu complex 3 exhibits no redox chemistry at the Nid site and no reaction with CO. In contrast, the Nip sites in 4 and 6 are readily reduced (characterized by their Ni(I) EPR spectra) and bind CO, exhibiting nuco bands at 2044 and 1997 cm-1, respectively, indicating terminal CO binding. The present Ni-Ni systems replicate the structural and chemical properties of the A-cluster site in ACS/CODH and support the presence of Ni at Mp in the catalytically active enzyme.

Acetate-CoA Ligase↗

PubMed2003

Structural model for an alkaline form of ferricytochrome C.

An (15)N-enriched sample of the yeast iso-1-ferricytochrome c triple variant (Lys72Ala/Lys79Ala/Cys102Thr) in an alkaline conformation was examined by NMR spectroscopy. The mutations were planned to produce a cytochrome c with a single conformer. Despite suboptimal conditions for the collection of spectra (i.e., pH approximately equal to 11), NMR remains a suitable investigation technique capable of taking advantage of paramagnetism. 76% of amino acids and 49% of protons were assigned successfully. The assignment was in part achieved through standard methods, in part through the identification of groups maintaining the same conformation as in the native protein at pH 7 and, for a few other residues, through a tentative analysis of internuclear distance predictions. Lys73 was assigned as the axial ligand together with His18. In this manner, 838 meaningful NOEs for 108 amino acids, 50 backbone angle constraints, and 203 pseudocontact shifts permitted the convergence of randomly generated structures to a family of conformers with a backbone RMSD of 1.5 +/- 0.2 A. Most of the native cytochrome c conformation is maintained at high pH. The NOE pattern that involves His18 clearly indicates that the proximal side of the protein, including the 20s and 40s loops, remains essentially intact. Structural differences are concentrated in the 70-80 loop, because of the replacement of Met80 by Lys73 as an axial ligand, and in the 50s helix facing that loop; as a consequence, there is increased exposure of the heme group to solvent. Based on several spectral features, we conclude that the folded polypeptide is highly fluxional.

Cytochromes c↗

PubMed2005

Development of a biosorbent for arsenite: structural modeling based on X-ray spectroscopy.

This work describes a biological route for direct sorption of aqueous As(III) species, which are the most toxic and mobile arsenic species found in soils. Based upon the biochemical mechanisms that explain arsenic toxicity, we propose that a waste biomass with a high fibrous protein content obtained from chicken feathers can be used for selective As(III) adsorption. Prior to adsorption, the disulfide bridges present in the biomass are reduced by thioglycolate. Our investigations demonstrated that As(III) is specifically adsorbed on the biomass and, contrary to the behavior observed with inorganic sorbents, the lower is the pH the more effective is the removal. Arsenic uptake reaches values of up to 270 micromol As(III)/g of biomass. Analyses by synchrotron light techniques, such as XANES, demonstrated that arsenic is adsorbed in its trivalent state, an advantage over conventional techniques for As uptake, which usually require a previous oxidation stage. EXAFS analyses showed that each As atom is directly bound to three S atoms with an estimated distance of 2.26 A. The uptake mechanism is explained in terms of the structural similarities between the As(III)-biomass complex structure and that of arsenite ions and Ars-Operon system encoded proteins and phytochelatins. The biological route presented here offers the perspective of a direct removal of arsenic in its reduced form.

Adsorption↗

PubMed2006

Sparkle/AM1 structure modeling of lanthanum (III) and lutetium (III) complexes.

The sparkle/AM1 model for the quantum chemical prediction of coordination polyhedron crystallographic geometries from isolated lanthanide complex ion calculations, defined recently for Eu(III), Gd(III), and Tb(III) (Inorg. Chem. 2005, 44, 3299) is now extended to La(III) and Lu(III). Thus, for each of the metal ions we chose a training set of 15 complexes that possess various representative ligands of high crystallographic quality (R factor < 0.05 Angstroms) and oxygen and/or nitrogen as coordinating atoms. In the validation procedure we used a set of 60 more La(III) coordination compound structures, as well as 15 more Lu(III) coordination compound structures, all of high crystallographic quality. For both the 75 La(III) compounds and the 30 Lu(III) compounds, the Sparkle/AM1 unsigned mean error, for all interatomic distances between the metal ions and the ligand atoms of the first sphere of coordination, is 0.08 Angstroms, thus comparable to the accuracy normally achievable by present day ab initio/ECP calculations, while being hundreds of times faster.

Journal Article↗

PubMed2004

Identification, expression, modeled structure and serological characterization of Plasmodium vivax histone 2B.

Histones play important role in DNA packaging, replication and gene expression. Here, we describe the isolation and characterization of histone 2B (PvH2B) gene from the most common but non-cultivable human malaria parasite Plasmodium vivax. The isolated cDNA clone of PvH2B was allowed to express in Escherichia coli and the recombinant protein was purified by affinity chromatography. The expressed PvH2B protein showed DNA-binding properties on the South-Western analysis and the confocal microscopy localized it in the parasite nucleus. This gene is actively expressed during blood stages of the parasite and all P. vivax patients produced antibodies against the protein. The mRNA of PvH2B was found to contain a poly(A) tail at its 3' end, unlike abundant mRNA of human H2B. The encoded polypeptide is 118 amino acid long contains a nuclear targeting site, a signature motif of H2B and showed 74% homology to its host molecule. The structure of PvH2B showed that it has certain differences from that of its host at critical functional sites (viz acetylation, methylation, trypsin cleavage, DNA-binding and inter-histone interaction) which are required for general gene expression and DNA packaging. The distinctive structural features of P. vivax H2B described here may help in designing the specific antimalarial drugs.

Amino Acid Sequence↗

PubMed1990

Structural model of porcine factor VIII and factor VIIIa molecules based on scanning transmission electron microscope (STEM) images and STEM mass analysis.

Porcine plasma factor VIII (fVIII) molecules are heterodimers composed of a 76,000-mol wt light chain (-A3-C1-C2) and a heavy chain ranging in molecular weight from 82,000 (A1-A2) to 166,000 (A1-A2-B). Proteolytic activation of fVIII by thrombin results in fVIIIa heterotrimers lacking B domains (A1, A2, A3-C1-C2). In this study, immunoaffinity purified fVIII was further fractionated by mono S or mono Q chromatography to prepare heterodimers containing a light chain and an A1-A2-B heavy chain (fVIII 166/76) or an A1-A2 heavy chain (fVIII 82/76). Mass analysis of scanning transmission electron microscopic (STEM) images of fVIII 166/76 indicated that heterodimers (mass 237 +/- 20 kD) had irregularly globular core structures 10-12 nm across, and frequently displayed a diffuse, occasionally globular to ovoid satellite structure extending 5-14 nm from the core, and attached to it by a thin stalk. Factor VIII 82/76 molecules (mass 176 +/- 20 kD) had the same core structures as fVIII 166/76 molecules, but lacked the satellite structure. These findings indicate that A1-A2 domains of heavy chains and the light chains of the fVIII procofactor molecule are closely associated and constitute the globular core structure, whereas the B domainal portion of heavy chains comprises the peripheral satellite appendage. Factor VIII core structures commonly displayed a finger-like projection near the origin of the B domainal stalk that was also a consistent feature of the free heavy chains (mass 128-162 kD) found in fVIII 166/76 preparations. Factor VIII light chain monomers (mass, 76 +/- 16 kD) were globular to c-shaped particles 6-8 nm across. These chains commonly possessed a v-shaped projection originating from its middle region, that could also be observed at the periphery of fVIII core molecules. Factor VIIIa preparations contained heterotrimers (mass 162 +/- 13 kD) that had the same dimensions as fVIII core structures, lacked the B domainal appendage, and sometimes possessed the same core features as fVIII molecules. Molecular species corresponding to heterodimers (mass, 128 +/- 13 kD) and unassociated subunit chains (40-100 kD) were also observed in fVIIIa preparations, suggesting that heterotrimers have an appreciable tendency to dissociate, a phenomenon that could explain the decay of fVIIIa activity after thrombin activation of fVIII.

Animals↗

PubMed1989

Functionally distinct agonist and receptor-binding regions in human chorionic gonadotropin. Development of a tertiary structure model.

The histidine residues in human chorionic gonadotropin (hCG) were chemically modified using diethyl pyrocarbonate. Derivatives of hCG with an average of 0.5-3.5 histidines modified (maximum of 4 per hCG) had reduced receptor-binding and cell-stimulating activities. Acylation of hCG at progressively lower pH values (conditions in which 1 of the 2 absolutely conserved histidines alpha His-83 is not titratable, whereas alpha His-94 becomes increasingly protonated and resistant to modification) produced hCG derivatives with a greater retention of receptor-binding activity than cell-stimulating activity. The involvement of alpha His-94 as part of the receptor-binding region of the hormone and of alpha His-83 as a putative active site residue was inferred. Proteinaceous protease inhibitors were shown to neutralize the agonist activity of hCG and to reduce the binding of hCG to its receptor and also to specific antisera. It was presumed that an inhibitor-hormone complex was formed which was analogous to the complexing of inhibitor with the "substrate pocket" of a serine protease. The discovery of primary sequence analogies between hCG and the serine protease chymotrypsin enabled the prediction of hCG structure using the enzyme as a folding template. Solvent-exposed and buried core regions of the peptide chain were delineated using smoothed hydrophobicity profiles in combination with Chou-Fasman secondary structure predictions. Hypervariable hydrophobicity indices between residues 38 and 80 of the human beta subunits reflected different folding arrangements which presumably conferred the individual receptor specificities. When mapped to the putative structure these receptor-determinant loops were adjacent to an area of the alpha subunit analogous to the substrate pocket of serine proteases. Disulfide bond assignments and intersubunit contact regions were identifiable. The proposed tertiary structure for hCG manifests the topographical epitopes defined using monoclonal antibodies and satisfies the currently available data on specific modification and its effects upon hormonal structure and function. This paper is considered to be the first report of a differential effect upon the agonist and receptor binding abilities of a glycoprotein hormone after modification of the proteinaceous, as opposed to the glycosylated, moiety of the molecule.

Amino Acid Sequence↗

PubMed2002

Modeling aerobic carbon source degradation processes using titrimetric data and combined respirometric-titrimetric data: experimental data and model structure.

Experimental data are presented that resulted from aerobic batch degradation experiments in activated sludge with simple carbon sources (acetate and dextrose) as substrates. Data collection was done using combined respirometric-titrimetric measurements. The respirometer consists of an open aerated vessel and a closed non-aerated respiration chamber for monitoring the oxygen uptake rate related to substrate degradation. The respirometer is combined with a titrimetric unit that keeps the pH of the activated sludge sample at a constant value by addition of acid and/or base. The experimental data clearly showed that the activated sludge bacteria react with consumption or production of protons during aerobic degradation of the two carbon sources under study. Thus, the cumulative amount of added acid and/or base could serve as a complementary information source on the degradation processes. For acetate, protons were consumed during aerobic degradation, whereas for dextrose protons were produced. For both carbon sources, a linear relationship was found between the amount of carbon source added and the amount of protons consumed (in case of acetate: 0.38 meq/mmol) or produced (in case of dextrose: 1.33 meq/mmol) during substrate degradation. A model taking into account substrate uptake, CO(2) production, and NH(3) uptake for biomass growth is proposed to describe the aerobic degradation of a C(x)H(y)O(z)-type carbon source. Theoretical evaluation of this model for reference parameters showed that the proton effect due to aerobic substrate degradation is a function of the pH of the liquid phase. The proposed model could describe the experimental observations with both carbon sources.

Acetates↗

PubMed2004

Molecular studies of anti-HLA-A2 using light-chain shuffling: a structural model for HLA antibody binding.

Human leukocyte antigen (HLA) A2 is one of the most immunodominant HLA antigens. Through a process of light-chain variable domain (VL) shuffling, we analyzed the VL domains' role in anti-HLA-A2/A28-binding site diversity. This was achieved by combining a VH3-30-encoded HLA-A2/A28-specific heavy-chain variable domain with 10(4) non-immune VL domains. Twelve HLA-A2/A28-specific antibodies were subsequently identified. VL gene analysis demonstrated an absence of Vlambda domains and that all have VkappaI-encoded light chains. The affinities correlated with the VkappaI gene present, with the seven highest affinity antibodies using Vkappa domains encoded by the O18 gene segment. A 300-fold difference in affinity was observed between the 12 antibodies, and homology modeling demonstrated a correlation between electrostatic surface potential of the antigen-binding site and affinity for HLA. Overlap between the T-cell receptor-binding site and that of the antibodies was indicated by inhibition of cytotoxic T-lymphocyte killing of peptide-pulsed target cells. A model of antibody binding to HLA-A2 suggested contact with both alpha helices of the HLA molecule, such that the antigen-binding site spans the peptide-binding groove. These data increase the understanding of antibody recognition of HLA and may facilitate the production of clonotypic antibodies with peptide-specific binding.

Antibodies, Monoclonal↗

PubMed1998

Lanthanide(III) Complexes of Tripodal N-Donor Ligands: Structural Models for the Species Involved in Solvent Extraction of Actinides(III).

The complexation of lanthanides(III) by the tripodal ligands tpa (tris[(2-pyridyl)methyl]amine) and tpza (tris[(2-pyrazinyl)methyl]amine) has been investigated by solution NMR studies and by X-ray crystallography. The crystallographic studies show that both tpa and the new ligand tpza form complexes with a 1:1 metal:ligand ratio in which the tripodal amine acts as a tetradentate ligand. For the tpa complexes the remaining coordination sites are occupied by chloride counterions to give 7-coordination (Eu, Tb, Lu) or by chloride counterions and a methanol molecule to give 8-coordination (Nd). In [Nd(tpza)(H(2)O)(3)(CH(3)CN)(3)](ClO(4))(3).3H(2)O the remaining coordination sites are occupied by water and acetonitrile molecules to give 10-coordination while the perchlorate counterions remain non coordinating. Tpza complexes have been isolated from acetonitrile solution and dissociate completely in methanol, while the complexes of the more basic tpa can be isolated from methanol and exist in water in equilibrium with the free ligand. Solvent extraction studies of lanthanides(III) and actinides(III) from nitric acid solutions show that the new ligand tpza is, unlike tpa, a selective complexant of actinides(III). Considering their structural analogy, this difference could be explained in terms of the electronic differences between the two ligands resulting in a stronger affinity of actinides(III) for the softer donor tpza.

Journal Article↗